Publications by authors named "Shao-Heng He"

68 Publications

Immunological characterization of the American cockroach allergen Per a 9 expressed in baculovirus-infected insect cells.

Cent Eur J Immunol 2019 30;44(3):322-326. Epub 2019 Sep 30.

Research Division of Clinical Pharmacology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

American cockroach (CR) allergy has been recognized as important IgE-mediated type I hypersensitivity. Per a 9 is an arginine kinase, reacting with IgE in sera of all CR allergic Thai patients. Per a 9 gene was cloned and expressed in eukaryotic systems (baculovirus-infected insect cells). The expressed Per a 9 was purified by Nickel column. The antigenicities were analyzed by ELISA, immunoblot analysis and basophile activation test. The results show that 13 out of 16 (81.3%) sera from American CR patients reacted to Per a 9, confirming that Per a 9 is a major allergen of CR. The IgE reactivity of Per a 9 in the sera from American CR patients was increased 8.3-fold in comparison with the sera from healthy controls. Per a 9 at 1.0 μg/ml induced an approximately up to 5.6-fold increase in CD63 and CCR3 double positive cells when incubating with passively sensitized basophils from by sera from American CR patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5114/ceji.2019.89611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925565PMC
September 2019

[Expression of LRG-1 in clinical specimens and Tca8113 cell line of tongue carcinoma].

Nan Fang Yi Ke Da Xue Xue Bao 2016 Mar;36(3):297-302

Department of Dentistry, First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001, China.E-mail:

Objective: To investigate the expression of LRG-1 in clinical specimens and Tca8113 cell line of tongue carcinoma and analyze the relationship between LRG-1 expression and the clinicopathological parameters.

Methods: LRG-1 expression was detected in 40 tongue squamous cell carcinoma (TSCC) tissues and paired normal adjacent tissues, 20 atypical hyperplasia tissues of the tongue, and 20 tissues of tongue cancer in situ using immunohistochemical method. The expression of LRG-1 in Tca8113 cell line was detected using flow cytometry. The expression of LRG-1 was also detected in human TSCC tissues and Tca8113 cells with Western blotting. The effect of LRG-1 on the proliferation of HUVECs was determined using MTT assay, and its effect on angiogenesis was evaluated with Matrigel tube formation assays.

Results: Human TSCC tissues had a significantly higher rate of positive expression for LRG-1 (85%, 34/40) than the adjacent tissues (10%, 4/40), invasive tongue cancer (30%, 6/20), and tongue cancer in situ (50%, 10/20) (P<0.05). LRG-1 expression was correlated with the degree of tumor differentiation, clinical stage and lymph node metastasis of the tumor (P<0.05) but not with the patients' age or gender. In the in vitro experiment, LRG-1 promoted HUVEC proliferation and angiogenesis.

Conclusion: Abnormal LRG-1 expression is present in the human TSCC tissue and Tca8113 cells. LRG-1 can promote HUVEC proliferation and angiogenesis in vitro, suggesting its possible role in promoting tumor angiogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2016

Mast cells and basophils are essential for allergies: mechanisms of allergic inflammation and a proposed procedure for diagnosis.

Acta Pharmacol Sin 2013 Oct 26;34(10):1270-83. Epub 2013 Aug 26.

1] Allergy and Clinical Immunology Research Centre, Liaoning Medical University, Jinzhou 121001, China [2] Clinical Research Centre, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

The current definition of allergy is a group of IgE-mediated diseases. However, a large portion of patients with clinical manifestations of allergies do not exhibit elevated serum levels of IgE (sIgEs). In this article, three key factors, ie soluble allergens, sIgEs and mast cells or basophils, representing the causative factors, messengers and primary effector cells in allergic inflammation, respectively, were discussed. Based on current knowledge on allergic diseases, we propose that allergic diseases are a group of diseases mediated through activated mast cells and/or basophils in sensitive individuals, and allergic diseases include four subgroups: (1) IgE dependent; (2) other immunoglobulin dependent; (3) non-immunoglobulin mediated; (4) mixture of the first three subgroups. According to our proposed definition, pseudo-allergic-reactions, in which mast cell or basophil activation is not mediated via IgE, or to a lesser extent via IgG or IgM, should be non-IgE-mediated allergic diseases. Specific allergen challenge tests (SACTs) are gold standard tests for diagnosing allergies in vivo, but risky. The identification of surface membrane activation markers of mast cells and basophils (CD203c, CCR3, CD63, etc) has led to development of the basophil activation test (BAT), an in vitro specific allergen challenge test (SACT). Based on currently available laboratory allergy tests, we here propose a laboratory examination procedure for allergy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/aps.2013.88DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4002163PMC
October 2013

A unique life-threatening mediastinal liposarcoma mimicking pleural effusion.

Am J Respir Crit Care Med 2012 Jul;186(1):106

Department of Respiratory Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1164/rccm.201109-1676IMDOI Listing
July 2012

IFN-λ inhibits HIV-1 integration and post-transcriptional events in vitro, but there is only limited in vivo repression of viral production.

Antiviral Res 2012 Jul 11;95(1):57-65. Epub 2012 May 11.

Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

The lambda interferons (IL-28a, 28b, and IL-29) inhibit the replication of many viruses, but their role in the inhibition of HIV-1 infection remains unclear. During this study, we monitored IL-29 production in HIV-1 infected individuals and analyzed the in vitro and in vivo inhibition of HIV-1 production. Prior treatment with IL-28a or IL-29 induced an antiviral state in cultured primary T-cells, which suppressed HIV-1 integration and post-transcriptional events. The antiviral factors MxA, OAS, and PKR were up-regulated. In HIV-1 infected patients, IL-29 level was increased along with the depletion of CD4⁺ T-cells in peripheral blood, while the elevated IL-29 did not show a significantly negative correlation with viral load. Further analysis of HIV-1 infected individuals showed that IL-29 was positively correlated with IFN-β and anti-inflammatory cytokine IL-10, and was negatively correlated with IFN-γ, which might suggest that IFN-λ participates in modulating antiviral immune responses during HIV-1 infection in vivo. Together, although IFN-λ impeded HIV-1 infection of T-cells in vitro, IFN-λ showed only limited in vivo repression of viral production. The modulation of IFN-λ on inflammatory factors might be worthy for further concentrating on for better understanding the host immune response during HIV-1 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.antiviral.2012.04.011DOI Listing
July 2012

Eosinophil-derived interferon-lambda contributes to initiation of allergen-related inflammation in the intestine.

Cytokine 2012 May 4;58(2):186-92. Epub 2012 Feb 4.

Clinical Experimental Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.

Background And Aims: Epithelial barrier dysfunction plays a critical role in the initiation of a number of immune diseases; the causative factors are not fully understood. The present study aimed to elucidate the mechanism by which the eosinophil-derived interferon (IFN)-lambda induced the gut epithelial barrier dysfunction.

Methods: The duodenal biopsies were obtained from patients with or without food allergies. The eosinophils and IFNλ expression were observed by immune staining. Intestinal epithelial cell line, T84 cells, and a mouse model were employed to observe the effect of IFNλ on the epithelial barrier function and the initiation of skewed T helper (Th)2 polarization in the mouse intestine.

Results: IFNλ expression was observed in over 80% human eosinophils of the subjects with or without food allergies. Exposure to microbial products, lipopolysaccharide or peptidoglycan, could induce eosinophils to release IFNλ. Exposure to IFNλ could induce intestinal epithelial barrier dysfunction via inducing the epithelial cell apoptosis. Concurrent exposure to microbial products and food antigens could induce aberrant antigen specific Th2 polarization and Th2 pattern inflammation in the intestine.

Conclusions: Eosinophils express IFNλ that can induce intestinal epithelial barrier dysfunction and promotes the initiation of the aberrant Th2 polarization in the intestine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cyto.2012.01.003DOI Listing
May 2012

[Signal transduction pathway for TNF-induced IL-6 release from mast cells].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2011 Aug;27(8):829-31

Department of Pathophysiology, Hainan Medical College, Haikou 571101, China.

Aim: To investigate the effect of TNF on release of IL-6, IL-10 and histamine from mast cells and to explore its potential signal transduction pathway.

Methods: After stimulation of various concentrations of TNF, the P815 cells were analyzed by cellular activation of signal ELISA(CASE) to detect phosphorylation of ERK, p38 and STAT3, and the supernatants were collected and analyzed by ELISA to quantify release of IL-6, IL-10 and histamine from the cells.

Results: Compared with the untreated control, increased IL-6 release was detected in TNF-stimulated P815 cells (P<0.05). Pretreatment of PD98059 or U0126 inhibited TNF-induced IL-6 release and ERK phosphorylation in P815 cells (P<0.05), whereas pretreatment of SB203580 or AG490 hardly affect IL-6 release, with little effect on phosphorylation of p38 and STAT3 respectively.

Conclusion: TNF induced IL-6 release from P815 cells may involve activation of ERK signalling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
August 2011

Interferon-λ mediates oral tolerance and inhibits antigen-specific, T-helper 2 cell-mediated inflammation in mouse intestine.

Gastroenterology 2011 Jul 16;141(1):249-58, 258.e1-2. Epub 2011 Apr 16.

Clinical Experimental Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China.

Background & Aims: Oral tolerance is an important component of gastrointestinal homeostasis, but mechanisms of its development are not fully understood. Loss of oral tolerance occurs during food allergen-related inflammation in the gastrointestinal tract. Interferon (IFN)-λ regulates immunity, but its role in oral tolerance is not clear. We investigated the role and the mechanism of IFN-λ in the development of oral tolerance and its effect on antigen-induced, T-helper (Th)-2 cell-mediated inflammation in the intestine.

Methods: Expression of IFN-λ and its receptor were analyzed by immunohistochemical, flow cytometric, or immunoblot analyses. Tolerogenic dendritic cells (DCs) and regulatory T cells were examined in vitro and in vivo. A mouse model of antigen-induced, Th2 cell-mediated intestinal inflammation was used to examine the role of IFN-λ and T cells in oral tolerance in the intestine.

Results: CD3+ cells expressed the IFN-λ receptor, which was up-regulated following antigen-specific or nonspecific activation. Interaction between IFN-λ and its receptor induced apoptosis of T cells and their subsequent phagocytosis by DCs. This led to the generation of tolerogenic DCs and T regulatory cells in vitro and in vivo. Passive transfer of IFN-λ-primed CD3+ cells inhibited Th2 cell-mediated inflammation in the intestine.

Conclusions: IFN-λ is involved in development and maintenance of oral tolerance in the intestines of mice; it might be used to suppress antigen-specific Th2 cell-mediated inflammation in patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2011.04.006DOI Listing
July 2011

[Induction of monocyte-derived dendritic cell differentiation by asthmatic serum in a transendothelial trafficking model].

Zhonghua Jie He He Hu Xi Za Zhi 2011 Mar;34(3):169-73

Department of Respiratory Medicine, the First Affiliated Hospital, Nanjing Medical University, China.

Objective: To explore the effect of asthmatic and healthy serum on differentiation and function of monocyte-derived dendritic cells (MDDC) in a transendothelial trafficking model.

Methods: The sera and peripheral blood mononuclear cells (PBMC) were separated from 12 asthmatic patients and 12 healthy volunteers, and monocytes were selected from PBMC using magnetic beads. The trypsin-digested human umbilical vein endothelial cells (HUVEC) at passage 2 from 5 healthy lying-in women were used to construct the transendothelial trafficking model under asthmatic or healthy serum, wherein MDDC were identified by silver nitrate staining and scanning electron microscopy. Nuclear factor κB (NF-κB) activity was determined by electrophoretic mobility shift assay. Flow cytometry, ELISA and mixed leukocyte reaction were relevantly utilized to detect the phenotype, cytokine and T cell proliferation.

Results: (1) Monocytes traversed through HUVEC monolayer after 2 h, and reverse-transmigrated to develop into DC 48 h later. (2) The healthy serum stimulated monocytes into immature MDDC with lower CD(14) [(20 ± 5)%] (F = 49.01, P < 0.05), and higher HLA-DR, CD(80), CD(86) and CD(83) [(43 ± 4)%, (17.9 ± 3.5)%, (43 ± 11)% and (6.7 ± 1.8)%, respectively] (F = 10.35 - 40.17, all P < 0.05) than monocytes did before transmigration at 0 h [CD(14) (81 ± 6)%, HLA-DR (24 ± 5)%, CD(80) (2.8 ± 2.0)%, CD(86) (14 ± 4)% and CD(83) (0.9 ± 0.8)%, respectively]. (3) The asthmatic serum stimulated monocytes into mature MDDC, characteristic of dendrites, with similar HLA-DR and CD(86) [(55 ± 6)% and (59 ± 12)%] (F = 15.29 and 35.97, all P > 0.05), higher CD(80) and CD(83) [(49.7 ± 10.2)% and (30.2 ± 6.8)%] (F = 4.01 and 20.68, all P < 0.05), accompanied by increased levels of NF-κB activity, IL-12 p70 and T cell proliferation [(100 ± 11)%, (568 ± 43) ng/L and (2033 ± 198) cpm, respectively] (F = 49.23 - 350.84, all P < 0.05) relative to the healthy serum-stimulated immature MDDC [(12 ± 3)%, (220 ± 35) ng/L and (952 ± 64) cpm, respectively].

Conclusion: The asthmatic serum induces mature MDDC in association with NF-κB overactivation in the transendothelial trafficking model, which provides a promising experimental platform for both investigation of immunological mechanisms in asthma and screening of novel anti-asthma drugs in vitro.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3760/cma.j.issn1001-0939.2011.03.004DOI Listing
March 2011

Unusual life-threatening Rosai-Dorfman disease of the trachea: role of NF-κB.

Thorax 2010 Oct;65(10):927-9

Department of Respiratory Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.

Rosai-Dorfman disease (RDD) is a rare non-neoplastic histioproliferative disorder characterised by painless lymphadenopathy, low fever, high erythrocyte sedimentation rate, leucocytosis and hypergammaglobulinaemia. Overactivity of nuclear factor κB (NF-κB) is linked with inflammatory, cancerous and autoimmune diseases. The first case is described of an unusual life-threatening RDD of the trachea with no lymphadenopathy at risk of suffocation in a 39-year-old Chinese woman. A diagnosis of RDD was made following CT scans, thoracotomy and histological examination. Gel shift assay revealed an essential role for NF-κB overactivity in RDD. The patient remains well with no evidence of progression without treatment. Histological confirmation should be sought in all cases as the clinical manifestation of RDD is similar to asthma or lung carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/thx.2010.139998DOI Listing
October 2010

Induction of inflammatory cell accumulation by TM-N49 and promutoxin, two novel phospholipase A(2).

Toxicon 2010 Sep 9;56(4):580-8. Epub 2010 Jun 9.

Clinical Experiment Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, PR China.

Local inflammation is a prominent characteristic of snakebite wound. Snake venom phospholipase A(2)s (PLA(2)s) are one of the main components which contribute to accumulation of inflammatory cells. We have isolated TM-N49 and promutoxin from Protobothrops mucrosquamatus venom and investigated their ability in induction of cell accumulation by using an in vivo mouse model. The results showed that both TM-N49 and promutoxin are potent stimuli for induction of neutrophil, lymphocyte, macrophage and eosinophil accumulation in the mouse peritoneum. The TM-N49- and promutoxin-induced inflammatory cell accumulation was inhibited by pretreatment of animals with cyproheptadine, terfenadine and Ginkgolide B, indicating that histamine and PAF is likely to contribute to the cells accumulation. Pre-injection of antibodies against adhesion molecules ICAM-1, CD18, CD11a and L-selectin showed that ICAM-1 is a key adhesion molecule of TM-N49- and promutoxin-induced lymphocyte, macrophage and eosinophil accumulation; CD18 and CD11a plays an important role in the migration of neutrophils, eosinophils and macrophages; and L-selectin is involved in the neutrophil and eosinophil accumulation. In conclusion, induction of inflammatory cell accumulation by TM-N49 and promutoxin confirms that group II PLA(2)s is pivotal stimulus for cell infiltration, through which they participate in the formation of snakebite inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxicon.2010.05.018DOI Listing
September 2010

Glucuronoxylomannan promotes the generation of antigen-specific T regulatory cell that suppresses the antigen-specific Th2 response upon activation.

J Cell Mol Med 2009 Aug;13(8B):1765-1774

Brain Body Institute and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.

T regulatory cells (Treg) have the capability to suppress the skewed immune response, but the generation of antigen (Ag)-specific Treg for therapeutic purpose is a challenge; the mechanism of Ag-specific Treg activation remains obscure. Here, we report that glucuronoxylomannan (GXM) is capable of promoting the development of human tolerogenic dendritic cells (DC). GXM-pulsed DCs increased the expression of forkhead box P3 (Foxp3) in naïve human CD4(+)CD25(-) T cells via activating Fc gamma receptor IIb and activator protein-1 and promoting the expression of transforming growth factor beta in dendritic cells. Furthermore, the conjugated complex of house dust mite Ag, Dermatophagoides pteronyssinus (Der p) 1, and GXM-pulsed DCs to drive the naïve human CD4(+)CD25(-) T cells to develop into the Der p 1-specific Tregs, which efficiently suppressed the Ag-specific Th2 responses. We conclude that GXM-conjugated specific Ag have the capacity to up-regulate the tolerogenic property of DCs and promote the generation of Ag-specific Tregs; the latter can be activated upon the re-exposure to specific Ag and suppress the skewed Ag-specific T helper (Th)2 responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1582-4934.2008.00583.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529965PMC
August 2009

Induction of microvascular leakage and histamine release by promutoxin, an Arg49 phospholipase A2.

Toxicon 2010 Apr 28;55(4):888-96. Epub 2009 Dec 28.

Clinical Experiment Center, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, PR China.

It has been recognized that phospholipase A(2) (PLA(2)) is a crucial factor of snake venom induced inflammation. Recently, promutoxin, a novel member of minor subgroup of snake venom PLA(2) (R49 PLA(2)) has been characterized in our laboratory, but its roles in induction of inflammation remain uninvestigated. Using highly purified promutoxin, we found this enzymatically inactive PLA(2) provoked a dose-dependent increase in microvascular leakage in the skin of rats. Pretreatment of rats with compound 48/80 diminished promutoxin-induced skin reaction and reduced mast cell numbers in rats. Cyproheptadine, terfenadine, Ginkgolide B and heparin inhibited promutoxin elicited microvascular leakage when they were co-injected with the stimulus to rat skin. Moreover, promutoxin was found to induce histamine release from human colon, lung and tonsil mast cells, and both metabolic inhibitors and pertussis toxin were capable of inhibiting promutoxin elicited histamine release. Provocation of microvascular leakage and mast cell activation by promutoxin suggests further that snake venom induced inflammation is related to mast cell activation and certain anti-inflammatory drugs could be therapeutic effective in treating snake wound.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxicon.2009.12.016DOI Listing
April 2010

Expression of integrin alphavbeta6 in the intestinal epithelial cells of patients with inflammatory bowel disease.

N Am J Med Sci 2009 Sep;1(4):200-4

Brain Body Institute, McMaster University, Hamilton, ON, Canada.

Background And Aims: The prevalence of inflammatory bowel disease (IBD) is about 0.05% in industrialized countries. The pathogenesis of IBD remains to be further understood. The present study aims to elucidate the expression of integrin αvβ6 in the intestinal mucosa of patients with IBD.

Materials And Methods: Colonic biopsy was obtained from a group of IBD patients. The expression of αvβ6 in the intestinal mucosa was detected by Western blotting. Human colonic epithelial cell line T84 cells were stimulated by microbial antigen flagellin. The expression of αvβ6 in T84 cells was evaluated by quantitative RT-PCR and Western blotting.

Results: The levels of αvβ6 in the intestinal mucosa were much lower than it in normal control subjects. The serum levels of myeloperoxidase (MPO) were higher in IBD patients that were negatively correlated with the levels of αvβ6 in the intestinal mucosa. The expression of αvβ6 was detectable in T84 cells at naοve status that could be upregulated by exposure to microbial antigen flagellin. Pretreatment with MPO dramatically suppressed the expression of αvβ6 in T84 cells.

Conclusions: We conclude that the expression of αvβ6 was suppressed in IBD intestinal mucosa, which could be resulted from the high levels of MPO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4297/najms.2009.4200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3364666PMC
September 2009

Targeted NF-kappaB inhibition of asthmatic serum-mediated human monocyte-derived dendritic cell differentiation in a transendothelial trafficking model.

Cell Immunol 2009 14;260(1):14-20. Epub 2009 Jul 14.

Department of Respiratory Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.

Transendothelial trafficking model mimics in vivo differentiation of monocytes into dendritic cells (DC). The serum from patients with systemic lupus erythematosus promotes the differentiation of monocytes into mature DC. We have shown that selective inhibition of NF-kappaB by adenoviral gene transfer of a novel mutated IkappaBalpha (AdIkappaBalphaM) in DC contributes to T cell tolerance. Here we demonstrated for the first time that asthmatic serum facilitated human monocyte-derived DC (MDDC) maturation associated with increased NF-kappaB activation in this model. Furthermore, selective blockade of NF-kappaB by AdIkappaBalphaM in MDDC led to increased apoptosis, and decreased levels of CD80, CD83, CD86, and IL-12 p70 but not IL-10 in asthmatic serum-stimulated MDDC, accompanied by reduced proliferation of T cells. These results suggest that AdIkappaBalphaM-transferred MDDC are at a more immature stage which is beneficial to augment the immune tolerance in asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cellimm.2009.07.001DOI Listing
November 2009

Induction of mast cell accumulation, histamine release and skin edema by N49 phospholipase A2.

BMC Immunol 2009 Apr 28;10:21. Epub 2009 Apr 28.

Clinical Experiment Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.

Background: It has been recognized that phospholipase A2 (PLA2) is a crucial component of snake venom, which contributes greatly to snake venom induced inflammation in man. However, the mechanisms through which N49 PLA2 provoke inflammation remain unclear. Recently, a N49 PLA2, TM-N49 from Protobothrops mucrosquamatus crude venom was characterized in our laboratory. Since the purification procedure developed is able to supply us with relatively large quantity of highly purified TM-N49, we investigated the ability of TM-N49 in induction of inflammation.

Results: The results showed that TM-N49 provoked a dose dependent increase in microvascular leakage in the skin of rats. The potency of TM-N49 in induction of skin edema appeared similar potency of bradykinin and histamine. Pretreatment of rats with compound 48/80 diminished TM-N49 induced skin reaction and reduced mast cell numbers in rats. Ginkgolide B and cyproheptadine, but not terfenadine and quinacrine, inhibited TM-N49 elicited microvascular leakage when they were co-injected with the stimulus to rat skin. Moreover, TM-N49 was found to induce histamine release from human colon, lung and tonsil mast cells, and both metabolic inhibitors and pertussis toxin were capable of inhibiting TM-N49 elicited histamine release. TM-N49 induced mast cell accumulation in the peritoneum of mice, which was inhibited by co-injection of ginkgolide B, cyproheptadine and terfenadine. Intravenous injection of monoclonal antibodies against CD18, ICAM-1 and CD11a also blocked TM-N49 induced mast cell accumulation.

Conclusion: TM-N49 is a potent stimulus for skin edema, mast cell activation and accumulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2172-10-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2681446PMC
April 2009

Purification, characterization and biological activities of the L-amino acid oxidase from Bungarus fasciatus snake venom.

Toxicon 2009 Sep 23;54(3):262-71. Epub 2009 Apr 23.

Clinical Research Centre, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.

L-amino acid oxidases (LAAOs) are widely distributed in snake venoms, which contribute to the toxicity of venoms. However, LAAO from Bungarus fasciatus (B. fasciatus) snake venom has not been isolated previously. In the present study, LAAO from B. fasciatus snake venom was purified by SP-Sepharose HP anion exchange chromatography followed by Heparin-Sepharose FF affinity chromatography procedure and the purified enzyme was named BF-LAAO. BF-LAAO presented an estimated molecular weight of 55kDa in SDS-PAGE and an apparent molecular weight of 70kDa in size-exclusion chromatography suggesting that BF-LAAO is a monomeric protein. Kinetics studies showed that BF-LAAO was very active against L-Tyr, L-Asp, L-Phe, L-Glu, L-Trp, L-His, L-Gln, L-Ile, L-Met, L-Leu and moderately active against L-Lys, L-Arg, L-Ala and L-Asn. BF-LAAO exhibited a cytotoxic effect on A549 cells and caused up to 41.2% apoptosis of A549 cells following 12h incubation period. In the mouse peritoneum, BF-LAAO provoked a marked increase in the number of neutrophils, lymphocytes and macrophages following injection. It also induced rabbit platelet aggregation in a dose-dependent manner. At 3h following injection, BF-LAAO elicited severe inflammation in the gastrocnemius muscles of mice, but failed to induce significant organ damage. In conclusion, the cytotoxic and proinflammatory activities of BF-LAAO could be the main cause of the local inflammation, which helps us to understand the pathogenesis of snakebite.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxicon.2009.04.017DOI Listing
September 2009

Disruption of T-cell immunoglobulin and mucin domain molecule (TIM)-1/TIM4 interaction as a therapeutic strategy in a dendritic cell-induced peanut allergy model.

J Allergy Clin Immunol 2008 Jul 10;122(1):55-61, 61.e1-7. Epub 2008 Jun 10.

Brain-Body Institute, McMaster University, Hamilton, Ontario, Canada.

Background: Recent reports indicate that dendritic cell (DC)-derived T-cell immunoglobulin and mucin domain molecule (TIM)-4 plays an important role in the initiation of T(H)2 polarization. This study aims to elucidate the mechanisms of peanut allergy mediated by microbial products and DCs and the relationship between peanut allergy and TIM4.

Methods: Mouse bone marrow-derived DCs (BMDCs) were generated and exposed to cholera toxin (CT) or/and peanut extract (PE) for 24 hours and then adoptively transferred to naive mice. After re-exposure to specific antigen PE, the mice were killed; intestinal allergic status was determined.

Results: Increased expression of TIM4 and costimulatory molecules was detected in BMDCs after concurrent exposure to CT and PE. Adoptively transferred CT/PE-conditioned BMDCs resulted in the increases in serum PE-specific IgE and skewed T(H)2 polarization in the intestine. Oral challenge with specific antigen PE induced mast cell activation in the intestine. Treating with Toll-like receptor 4 small interfering RNA abolished increased expression of TIM4 and costimulatory molecules by BMDCs. Pretreatment with anti-TIM1 or anti-TIM4 antibody abolished PE-specific T(H)2 polarization and allergy in the intestine.

Conclusion: Concurrent exposure to microbial product CT and food antigen PE increases TIM4 expression in DCs and promotes DC maturation, which plays an important role in the initiation of PE-specific T(H)2 polarization and allergy in the intestine. Modulation of TIM4 production in DCs represents a novel therapeutic approach for the treatment of peanut allergy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2008.04.036DOI Listing
July 2008

Induction of inflammatory cytokine release from human umbilical vein endothelial cells by agonists of proteinase-activated receptor-2.

Clin Exp Pharmacol Physiol 2008 Jan;35(1):89-96

Allergy and Inflammation Research Institute, Key Immunopharmacology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, Guangdong, China.

1. Human endothelial cells express proteinase-activated receptor-2 (PAR-2), inflammatory cytokines and trypsin (EC 3.4.21.4). However, little is known about the mechanism through which trypsin induces cytokine release from endothelial cells. 2. In the present study, we investigated the effect of trypsin on cytokine release from primary cultures of human umbilical vein endothelial cells (HUVEC) using an antibody based protein microarray and ELISA. 3. The results showed that 1 microg/mL trypsin induced release of 32 different inflammatory factors, whereas 100 micromol/L Ser-Leu-Ile-Gly-Lys-Val-NH2 (SLIGKV-NH2) only stimulated secretion of 16 inflammatory factors from HUVEC, as assessed by an antibody based protein microarray. Because the release of interleukin (IL)-1a, IL-8, IL-10 and IL-12 was markedly increased following PAR-2 activation, their release was investigated further using ELISA. Increases in release of up to approximately 4.8-, 4.3-, 4.1- and 1.8-fold were observed for IL-1a, IL-10, IL-12 and IL-8, respectively, when HUVEC were challenged with trypsin for 16 h. Agonist peptides of PAR-2, namely SLIGKV-NH2 and trans-cinnamoyl-Leu-Ile-Gly-Arg-Leu-Orn-NH2 (tc-LIGRLO-NH2), also provoked significant release of IL-8. Trypsin-induced cytokine release was inhibited by its inhibitors soybean trypsin inhibitor, alpha1-antitrypsin and the inhibitor peptide of PAR-2 Phe-Ser-Leu-Leu-Arg-Tyr-NH2 (FSLLRY-NH2). 4. These data indicate the action of trypsin on HUVEC is most likely through activation of PAR-2, suggesting that PAR-2-related mechanisms are involved in the inflammatory process in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1440-1681.2007.04755.xDOI Listing
January 2008

[Prokaryotic expression of human mast cell chymase gene and preparation of its polyclonal antibody].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2007 Nov;23(11):1025-7

Department of Clinical Immunology, Guangdong Medical College, Zhanjiang 524023, China.

Aim: To express the human mast cell chymase cDNA in E.coli and prepare the antibody against human mast cell chymase with recombinant chymase.

Methods: The human mast cell chymase cDNA was cloned by RT-PCR. The recombinant chymase was expressed in E.coli with L-Arabinose induction and purified by Ni-NTA agarose column. Then the purified chymase was used as immunogen to immunize the rabbit. The titer and specificity of the anti-chymase antibody from the rabbit were analyzed by indirect ELISA and Western blot, respectively.

Results: The recombinant chymase was successfully expressed in E.coli, and the polyclonal anit-chymase antibody was prepared by immunizing the rabbit with the purified recombinant chymase. The titer of the generated antiserum was detected to be 1:12 800 by ELISA. Western blot analysis showed this antibody bound specifically with chymase.

Conclusion: The anti-chymase antibody from the rabbit with high titer and specificity has been prepared with purified recombinant chymase as immunogen, which lays a foundation for further research into detection and function of chymase.
View Article and Find Full Text PDF

Download full-text PDF

Source
November 2007

Evaluation of FORS-D analysis: a comparison with the statistically significant stem-loop potential.

Biochem Genet 2008 Feb 23;46(1-2):29-40. Epub 2007 Oct 23.

Department of Biochemistry and Molecular Biology, Jiangsu University School of Medical Technology, Zhenjiang, Jiangsu, P.R. China.

The stem-loop potential of a nucleic acid segment (expressed as a FONS value), decomposes into base composition-dependent and base order-dependent components. The latter, expressed as a FORS-D value, is derived by subtracting the value of the base composition-dependent component (FORS-M) from the FONS value. FORS-D analysis is the use of FORS-D values to estimate the potential of local base order to contribute to a stem-loop structure, and it has been used to investigate the relationship between stem-loop structure and other selective pressures on genomes. In the present study, we evaluated the reliability of FORS-D analysis by comparing it with statistically significant stem-loop potential, another robust method developed by Le and Maizel for examining stem-loop structure. We found that FORS-M values calculated using 10 randomized sequences are as reliable as those calculated using 100 randomized sequences. The resulting FORS-D values have a similar trend and distribution as statistically significant stem-loop potential, implying that FORS-D analysis is as reliable as the latter in measuring the distribution of base order-dependent stem-loop potential. Since the calculation of the FORS-M values is time consuming, the integrated program Bodslp developed by us will become a convenient tool for large-scale FORS-D analysis. The results also suggest that for some purposes the online program SigStb developed by Le and Maizel may be used as an alternative tool for FORS-D analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10528-007-9126-6DOI Listing
February 2008

Investigation into the signal transduction pathway via which heat stress impairs intestinal epithelial barrier function.

J Gastroenterol Hepatol 2007 Nov;22(11):1823-31

Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.

Background And Aims: Intact protein absorption is thought to be a causative factor in several intestinal diseases, such as food allergy, celiac disease and inflammatory bowel disease. However, the mechanism remains unclear. The aim of this study was to characterize a novel signal transduction pathway via which heat stress compromises intestinal epithelial barrier function.

Methods: Heat stress was carried out by exposing confluent human intestinal epithelial cell line T84 cell monolayers to designated temperatures (37-43 degrees C) for 1 h. Transepithelial electric resistance (TER) and permeability to horseradish peroxidase (HRP, molecular weight = 44 000) were used as indicators to assess the intestinal epithelial barrier function. Phosphorylated myosin light chain (MLC), MLC kinase (MLCK) and protein kinase C (PKC) protein of the T84 cells were evaluated in order to identify the signal transduction pathway in the course of heat stress-induced intestinal epithelial barrier dysfunctions.

Results: The results showed that exposure to heat stress significantly increased intact protein transport across the intestinal epithelial monolayer; the amount of phospho-PKC, phospho-MLCK and phospho-MLC proteins in T84 cells decreased significantly at 41 degrees C and 43 degrees C although they increased at 39 degrees C. The heat stress-induced T84 monolayer barrier dysfunction was inhibited by pretreatment with PKC inhibitor, MLCK inhibitor, or HSP70.

Conclusion: Heat stress can induce intestinal epithelial barrier dysfunction via the PKC and MLC signal transduction pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1440-1746.2006.04710.xDOI Listing
November 2007

Purification, characterization and potent lung lesion activity of an L-amino acid oxidase from Agkistrodon blomhoffii ussurensis snake venom.

Toxicon 2007 Dec 8;50(8):1126-39. Epub 2007 Aug 8.

Allergy and Inflammation Research Institute, The Key Immunopharmacology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xin-ling Road, Shantou, Guangdong 515041, China.

L-amino acid oxidases (LAOs) are one of the major components of snake venoms, which possess numerous biological functions. However, little is known of the influence of LAOs on organ lesions. In the present study, a unique LAO from Agkistrodon blomhoffii ussurensis snake venom named ABU-LAO was purified by Heparin-Sepharose FF chromatography followed by an ion-exchange chromatography procedure. The purified ABU-LAO appears a dimer with a molecular mass of approximately 108.8kDa. Kinetics studies showed that ABU-LAO is very active towards its substrates L-Asn, L-Phe, L-Tyr, L-Leu, L-Ile and L-Trp. The most striking observation in the present study is that ABU-LAO causes severe pneumorrhagia, pulmonary interstitial edema, fusion of pulmonary alveoli, cardiac interstitial edema and bleeding when being intravenously injected into BALB/c mice. ABU-LAO also induces liver cell necrosis and release of cytokines including IL-6, IL-12 and IL-2 from highly purified human peripheral blood monocytes and T cells, respectively. In conclusion, ABU-LAO potently induces lesions in lungs and livers. The ability of ABU-LAO will contribute to the understanding of the pathogenesis of snakebite wound.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxicon.2007.07.022DOI Listing
December 2007

[Preparation and characterization of rabbit antibody against human mast cell carboxypeptidase].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2007 Sep;23(9):859-61

Department of Clinical Immunology, Guangdong Medical College, Zhanjiang 524023, China.

Aim: To prepare antibody against human mast cell carboxypeptidase (hMC-CP) by using recombinant hMC-CP expressed in E.coli, and to characterize the antibody.

Methods: hMC-CP was expressed in E.coli with L-Arabinose induction and purified through Ni-NTA column. The purified hMC-CP as immunogen was used to immunize rabbit. The titer and the specificity of the rabbit anti-hMC-CP antibody was analyzed by indirect ELISA and Western blot respectively.

Results: The hMC-CP was successfully expressed and purified. The polyconal anit-hMC-CP antibody was prepared by immunizing rabbit using the purified recombinant protein, The titer of the generated antiserum was 1:6 400 by ELISA. Western blot analysis showed that this antibody could bind with hMC-CP specifically.

Conclusion: The rabbit anti-hMC-CP antibody with high titer and high specificity has been prepared by using purified recombinant hMC-CP as immunogen, which lays the foundation for further research on detection and function of hMC-CP.
View Article and Find Full Text PDF

Download full-text PDF

Source
September 2007

Mast cells play a crucial role in Staphylococcus aureus peptidoglycan-induced diarrhea.

Am J Pathol 2007 Aug 28;171(2):537-47. Epub 2007 Jun 28.

Department of Pathology, McMaster University, Hamilton, Ontario, Canada.

Bacterium-induced diarrhea results in 2 to 2.5 million deaths in the world each year. The mechanism needs to be further understood. Staphylococcus aureus infection has a close relation with diarrhea; its cell wall component peptidoglycan (PGN) has strong biological activity on immune cells and possibly plays a role in S. aureus-induced diarrhea. The present study showed that oral PGN-induced diarrhea in mice in a dose-dependent manner. Intestinal epithelial cells absorbed PGN via the intracellular pathway. Intestinal mast cells were activated after PGN gavage. Toll-like receptor (TLR)2 expression was detected in mast cells in the intestine as well as in the murine mast cell line p815 cells. Blocking TLR2 or nucleotide-binding oligomerization domain (NOD)1 with related antibodies or RNA interference abolished PGN-induced p815 cell activation. The mast cell mediator histamine and serotonin had synergistic effects in PGN-induced diarrhea. In summary, oral PGN can induce diarrhea in mice, and TLR2 and NOD1 mediate the PGN-induced mast cell activation that plays a critical role in diarrhea induction. Blockade of TLR2 or NOD1 or treating mice with a mast cell stabilizer can efficiently inhibit PGN-induced-diarrhea, providing potential therapeutic significance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2353/ajpath.2007.061274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1934528PMC
August 2007

Bacterial peptidoglycan breaks down intestinal tolerance via mast cell activation: the role of TLR2 and NOD2.

Immunol Cell Biol 2007 Oct 12;85(7):538-45. Epub 2007 Jun 12.

Pathology & Molecular Medicine, McMaster University, Hamilton, ON, Canada.

Intestinal microbes are believed to be involved in the pathogenesis of inflammatory bowel disease. Microbes and their products are generally well tolerated by intestinal epithelial cells in the intestinal tract of healthy individuals. It is of significance to understand what breaks down the established tolerance leading to intestinal barrier dysfunction and intestinal inflammation. T84 monolayer transported peptidoglycan (PGN) was determined by enzyme-linked immune assay. Mast cell line HMC-1 cell activation in response to PGN stimulation was observed with electron microscopy and measurement of histamine release. T84 monolayer barrier function was determined by recording the transepithelial electric resistance (TER) and measuring the permeability in response to PGN-induced HMC-1 cell activation. Expression of Toll-like receptor (TLR) 2 and nucleotide-binding oligomerization domain (NOD) 2 were determined by immunocytochemistry, real-time reverse transcription (RT)-PCR and Western blot. Exposure to PGN alone did not alter TER and permeability of T84 monolayers. T84 monolayers transported PGN from the apical chamber to the basal chamber of transwell system. TLR2 expressed on the surface of HMC-1 cells. HMC-1 cells absorbed PGN. HMC-1 cells released histamine in response to the PGN stimulation, which was blocked by pretreatment with antibodies or small interfering RNA against TLR2 or NOD2. In a co-culture system, T84 monolayer transported PGN activated HMC-1 cells and increased the horseradish peroxidase flux. TLR2 mediated the PGN-absorption in HMC-1 cells. Blockade of TLR2 or NOD2 abolished PGN-induced HMC-1 cell activation and T84 monolayer barrier dysfunction. T84 monolayer transported PGN activates HMC-1 cells to release chemical mediators to induce T84 monolayer dysfunction that are mediated by TLR2 and NOD2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/sj.icb.7100079DOI Listing
October 2007

Staphylococcal enterotoxin B increases TIM4 expression in human dendritic cells that drives naïve CD4 T cells to differentiate into Th2 cells.

Mol Immunol 2007 Jul 17;44(14):3580-7. Epub 2007 Apr 17.

Allergy Research Unit, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.

Aberrant T helper (Th)2 polarization plays a critical role in the pathogenesis of allergic disorders; the etiology remains unclear. Dendritic cells (DCs) express T cell immunoglobulin mucin domain (TIM)4 that ligates TIM1 on CD4 T cells to drive them to become Th2 cells, but the pathogenic source of TIM4 is unknown. Here we report that a significant increase in TIM4 expression in human DCs was observed in response to Staphylococcal enterotoxin B (SEB) stimulation via Toll-like receptor (TLR)2 and nucleotide-binding oligomerization domain (NOD)1 pathway. Coculture SEB-conditioned DCs with naïve CD4 T cells induced Th2 responses that could be abolished using TLR2 or NOD1 or TIM4 or TIM1 with counterpart antibodies or RNA interference. The results demonstrate that Staphylococcus aureus derived SEB promotes the TIM4 production in human DCs. The interaction between TIM4 and TIM1 drives naïve CD4 T cells to develop to Th2 cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molimm.2007.03.004DOI Listing
July 2007

Adaptive evolution of the spike gene of SARS coronavirus: changes in positively selected sites in different epidemic groups.

BMC Microbiol 2006 Oct 4;6:88. Epub 2006 Oct 4.

Department of Biochemistry and Molecular Biology, Jiangsu University School of Medical Technology, Zhenjiang, Jiangsu 212001, China.

Background: It is believed that animal-to-human transmission of severe acute respiratory syndrome (SARS) coronavirus (CoV) is the cause of the SARS outbreak worldwide. The spike (S) protein is one of the best characterized proteins of SARS-CoV, which plays a key role in SARS-CoV overcoming species barrier and accomplishing interspecies transmission from animals to humans, suggesting that it may be the major target of selective pressure. However, the process of adaptive evolution of S protein and the exact positively selected sites associated with this process remain unknown.

Results: By investigating the adaptive evolution of S protein, we identified twelve amino acid sites (75, 239, 244, 311, 479, 609, 613, 743, 765, 778, 1148, and 1163) in the S protein under positive selective pressure. Based on phylogenetic tree and epidemiological investigation, SARS outbreak was divided into three epidemic groups: 02-04 interspecies, 03-early-mid, and 03-late epidemic groups in the present study. Positive selection was detected in the first two groups, which represent the course of SARS-CoV interspecies transmission and of viral adaptation to human host, respectively. In contrast, purifying selection was detected in 03-late group. These indicate that S protein experiences variable positive selective pressures before reaching stabilization. A total of 25 sites in 02-04 interspecies epidemic group and 16 sites in 03-early-mid epidemic group were identified under positive selection. The identified sites were different between these two groups except for site 239, which suggests that positively selected sites are changeable between groups. Moreover, it was showed that a larger proportion (24%) of positively selected sites was located in receptor-binding domain (RBD) than in heptad repeat (HR)1-HR2 region in 02-04 interspecies epidemic group (p = 0.0208), and a greater percentage (25%) of these sites occurred in HR1-HR2 region than in RBD in 03-early-mid epidemic group (p = 0.0721). These suggest that functionally different domains of S protein may not experience same positive selection in each epidemic group. In addition, three specific replacements (F360S, T487S and L665S) were only found between 03-human SARS-CoVs and strains from 02-04 interspecies epidemic group, which reveals that selective sweep may also force the evolution of S genes before the jump of SARS-CoVs into human hosts. Since certain residues at these positively selected sites are associated with receptor recognition and/or membrane fusion, they are likely to be the crucial residues for animal-to-human transmission of SARS-CoVs, and subsequent adaptation to human hosts.

Conclusion: The variation of positive selective pressures and positively selected sites are likely to contribute to the adaptive evolution of S protein from animals to humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2180-6-88DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1609170PMC
October 2006

Rhinosinusitis derived Staphylococcal enterotoxin B plays a possible role in pathogenesis of food allergy.

BMC Gastroenterol 2006 Aug 18;6:24. Epub 2006 Aug 18.

Institute of Allergy and Department of Otolaryngology, First Hospital, Shanxi Medical University, Taiyuan, China.

Background: Staphylococcal enterotoxin B (SEB) is a potent immunomodulator and implicated with pathogenesis of inflammatory diseases mediated by Th1 or Th2 dominant immune responses. The objective of this study is to determine a possible association between rhinosinusitis derived SEB and pathogenesis of food allergy (FA).

Methods: The study included chronic rhinosinusitis (CRS) patients with FA (N = 46) or without FA (N = 33). Controls included FA patients without CRS (N = 26) and healthy volunteers (N = 25). In CRS patients, we assessed the parameters associated with FA including prick skin test (PST) reactivity to food allergens, serum levels of allergen-specific IgE and cytokines (IL-4, IL-13, IFN-I3), and the number/reactivity of food-allergen specific Th1/Th2 cells in the peripheral blood before and 2 months after sinus surgery. Changes of these parameters were evaluated in comparison with changes in SEB concentration in the sinus lavage and stool samples and also in vitro reactivity to SEB. In CRS patients with FA, we also assessed changes in reactivity to oral challenge of offending food before and after sinus surgery.

Results: Two months following sinus surgery, we observed statistically significant reduction in PST and oral challenge reactivity in CRS patients with FA in parallel to decrease in serum levels of Th2 cytokines (IL-4 and IL-13) and allergen specific IgE. Improvement of reactivity to food allergens was positively associated with decline in SEB concentrations in the sinus lavage and stool samples. In vitro study results also indicated a role of SEB in aggravation of Th2 skewed responses to food allergens. Such changes were not observed in CRS-non FA patients or control FA patients.

Conclusion: The rhinosinusitis derived SEB plays a certain role in the pathogenesis of FA by augmenting and/or maintaining polarized Th2 responses. Removal of SEB-producing pathogens from the rhinosinuses may be beneficial for attenuating the FA symptoms in patients with CRS-FA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-230X-6-24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1559701PMC
August 2006

Purification, characterization and cytokine release function of a novel Arg-49 phospholipase A(2) from the venom of Protobothrops mucrosquamatus.

Biochimie 2006 Oct 14;88(10):1331-42. Epub 2006 Jun 14.

Allergy and Inflammation Research Institute, The Shantou University Medical College, Xinling Road 11, 515031 Shantou, Guangdong, China.

Group IIA phospholipase A(2) (PLA(2)) are major components in Viperidae/Crotalidae venom. In the present study, a novel PLA(2) named promutoxin with Arg at the site 49 has been purified from the venom of Protobothrops mucrosquamatus by chromatography. It consists of 122 amino acid residues with a molecular mass of 13,656 Da assessed by MALDI-TOF. It has the structural features of snake venom group IIA PLA(2)s, but has no PLA(2) enzymatic activity. Promutoxin shows higher amino acid sequence identity to the K49 PLA(2)s (72-95%) than to D49 PLA(2)s (52-58%). Promutoxin exhibits potent myotoxicity in the animal model with as little as 1 microg of promutoxin causing myonecrosis and myoedema in the gastrocnemius muscle of mice. Promutoxin is also able to stimulate the release of IL-12, TNFalpha, IL-6 and IL-1beta from human monocytes, and induce IL-2, TNFalpha and IL-6 release from T cells, indicating that this snake venom group IIA PLA(2) is actively involved in the inflammatory process in man caused by snake venom poisoning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biochi.2006.05.003DOI Listing
October 2006