Publications by authors named "Eisa Salehi"

34 Publications

SP-A and TLR4 localization in lung tissue of SM-exposed patients.

Int Immunopharmacol 2020 Mar 11;80:105936. Epub 2019 Nov 11.

Immunoregulation Research Center, Shahed University, Tehran, Iran; Department of Immunology, Shahed University, Tehran, Iran. Electronic address:

Introduction: Long-term pulmonary complications are one of the major long-term consequences of sulfur mustard (SM) exposure. Toll-like receptor 4 (TLR4) involves in the pathogenesis of several pulmonary disorders. Surfactant protein-A (SP-A) regulates LPS-induced TLR4 localization and activation responses. However, the intensity and significance of TLR4 and SP-A expression by lung cells in SM-exposed patients is not clear.

Methods: The gene expression of TLR4 (through real-time PCR) and TLR4 and SP-A positive cells and alveolar type II cells, as SP-A producers, (using IHC) were assessed in formalin fixed paraffin embedded (FFPE) specimens from SM-exposed (n = 17), and non-SM exposed individuals (n = 12).

Results: TLR4 gene expression did not change between study groups. However, its cell surface presentation was significantly reduced in SM-exposed patients and particularly in which with constrictive bronchiolitis compared with the control group (P < 0.001 and P = 0.002, respectively). Frequency of alveolar type II cells was lower in the case group rather than the control group while the number of SP-A positive cells did not alter.

Conclusions: These findings suggest that reduced TLR4 cell surface presentation may have anti-inflammatory function and SP-A may have a critical role in regulation of inflammatory responses in SM-exposed patients. Further investigation on other possible mechanisms involved in TLR4 internalization maybe help to illustrate the modulatory or inflammatory activity of TLR4 in these patients.
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http://dx.doi.org/10.1016/j.intimp.2019.105936DOI Listing
March 2020

Inducible and endothelial nitric oxide synthase distribution and expression with hind limb per-conditioning of the rat kidney.

Arch Med Sci 2019 Jul 20;15(4):1081-1091. Epub 2019 Jun 20.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: We recently reported that a series of brief hind limb ischemia and reperfusion (IR) at the beginning of renal ischemia (remote per-conditioning - RPEC) significantly attenuated the ischemia/reperfusion-induced acute kidney injury. In the present study, we investigated whether the nitric oxide synthase (NOS) pathway is involved in the RPEC protection of the rat ischemic kidneys.

Material And Methods: Male rats were subjected to right nephrectomy and randomized as: (1) sham, no additional intervention; (2) IR, 45 min of renal ischemia followed by 24 h reperfusion; (3) RPEC, four 5 min cycles of lower limb IR administered at the beginning of renal ischemia; (4) RPEC+L-NAME (a non-specific NOS inhibitor, 10 mg/kg, .) (5) RPEC + 1400W (a specific iNOS inhibitor, 1 mg/kg, .). After 24 h, blood, urine and tissue samples were collected.

Results: The protective effect of RPEC on renal function, oxidative stress indices, pro-inflammatory marker expression and histopathological changes of kidneys subjected to 45 min ischemia were completely inhibited by pretreatment with L-NAME or 1400W. It was accompanied by increased iNOS and eNOS expression in the RPEC group compared with the IR group.

Conclusions: These findings suggest that the protective effects of RPEC on renal IR injury are closely dependent on the nitric oxide production after the reperfusion and both eNOS and iNOS are involved in this protection.
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http://dx.doi.org/10.5114/aoms.2019.85651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657261PMC
July 2019

Circulating mesenchymal stem cells in sulfur mustard-exposed patients with long-term pulmonary complications.

Toxicol Lett 2019 Sep 13;312:188-194. Epub 2019 May 13.

Department of Biostatistics and Social Medicine, Zanjan University of Medical Sciences, Zanjan, Islamic Republic of Iran.

Sulfur mustard (SM) is a toxic agent that causes acute and long-term pulmonary complications. Recent evidence has shown the impact of SM on mesenchymal stem cells (MSCs). These cells have a critical role in repairing the damaged tissues. In this study, we evaluated the mobilization of MSCs in SM-exposed patients with long-term pulmonary complications. Fifty-nine SM-injured patients with prolonged pulmonary complications and 20 healthy individuals were included. Patients were classified based on taking drugs, having comorbidities, and severity of respiratory consequence. MSCs with phenotype of CD45-CD44CD29CD105 were evaluated in peripheral blood using flow cytometry. Circulating MSCs were lower in SM-exposed patients compared to the control group (0.93 vs. 2.72 respectively, P = 0.005). No significant difference was observed in the MSC count between patients taking corticosteroids or antibiotics and those patients not taking them. Comorbidities like liver and kidney diseases had changed the count of MSCs in SM-exposed subjects. In addition, the frequency of MSCs did not show any association with the severity of long-term pulmonary complications. In conclusion, SM-exposure causes a decline in the frequency of circulating MSCs in survivors. The lower number of the peripheral MSC population in SM-exposed patients was not affected by taking corticosteroids or antibiotics, but comorbidities are probably involved in MSC frequency. The decreases observed in the number of circulating MSCs was not associated with the severity of the pulmonary complications; however, further studies in mustard lung models are required to demonstrate the therapeutic or pathologic role of MSCs in SM injuries.
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http://dx.doi.org/10.1016/j.toxlet.2019.05.015DOI Listing
September 2019

Effects of Probiotic Yogurt on Serum Omentin-1, Adropin, and Nesfatin-1 Concentrations in Overweight and Obese Participants Under Low-Calorie Diet.

Probiotics Antimicrob Proteins 2019 12;11(4):1202-1209

Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.

Data on the effects of probiotics on adipokines such as omentin-1, nesfatin-1, and adropin are limited. The aim of this study was to evaluate the effects of probiotic yogurt along with a low-calorie diet (LCD) on serum omentin-1, adropin, and nesfatin-1 concentrations in obese and overweight individuals. Sixty obese or overweight individuals aged 20-50 years old were involved in this randomized double-blind placebo-controlled clinical trial. Participants were randomly allocated into two groups to consume either probiotic yogurt containing Lactobacillus acidophilus La5, Bifidobacterium BB12, and Lactobacillus casei DN001 (10 CFU/g each) (n = 30) or regular yogurt (n = 30) along with a LCD in both groups for 8 weeks. Fasting blood samples were taken at baseline and after the 8-week intervention to determine related variables. A significant decrease in body fat percentage was observed in the probiotic group compared with the regular group after 8 weeks (- 1.51 ± 069 vs - 0.88 ± 0.68%, P = 0.002). After the 8-week intervention, a significant difference in serum adropin concentration (6.04 ± 24.46 vs - 8.16 ± 24.66 pg/ml, P = 0.03 and serum omentin-1 concentration (0.09 ± 1.51 vs - 1.5 ± 1.8 ng/ml, P = 0.003) was observed between two groups. We did not observe any significant changes in nesfatin-1 and other anthropometric measures. Overall, probiotic yogurt for 8 weeks among overweight or obese individuals along with LCD had beneficial effects on body fat percentage, serum omentin-1, and adropin concentration, but it did not have any effect on nesfatin-1 level.
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http://dx.doi.org/10.1007/s12602-018-9470-3DOI Listing
December 2019

Effect of MicroRNA-21 Transfection on In-vitro Differentiation of Human Naive CD4+ T Cells to Regulatory T Cells.

Iran J Allergy Asthma Immunol 2017 Jun;16(3):235-244

Immunology Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Regulatory T cells (Tregs) are important components of the immune system that modulate responses of other cells. These cells are involved in peripheral tolerance mechanisms, so defect in development and function of these cells can result in autoimmune disease. Increasing evidence supports the role of microRNAs-21 (miR-21) in the regulation of forkhead box P3 (Foxp3) expression in Tregs. We aimed to determine whether miR-21 transfection to naive CD4+ T cells can be useful in generation of iTregs in-vitro. We investigated in-vitro differentiation of miR-21-transfected naive CD4+ T cells to iTregs and compared these iTregs to cytokine-differentiated iTregs and control group. We showed that expression of Foxp3, transforming growth factor beta (TGF-β), and interleukin-10 (IL-10) are increased in iTregs generated after miR-21 transfection in comparison with cytokine-differentiated iTregs and control group. Our findings demonstrate that miR-21 has positive role in in-vitro generation of induced regulatory T-cells (iTregs).
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June 2017

Evaluation of TLR9 expression on PBMCs and CpG ODN-TLR9 ligation on IFN-α production in SLE patients.

Immunopharmacol Immunotoxicol 2017 Feb 3;39(1):11-18. Epub 2017 Jan 3.

e Department of Immunology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.

Context: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by autoreactive antibodies. Recent findings revealed the importance of innate immune responses, especially Toll-like receptors (TLRs) in the pathogenesis of SLE.

Objective: In this study, the level of TLR9 expression on peripheral blood mononuclear cells (PBMCs) was analyzed. The levels of produced IFN-α were also measured in supernatant of PBMCs from SLE patients and healthy controls after stimulation with CpG ODN2216 which is a plasmocytoid dendritic cell (pDC)-specific TLR9 ligand.

Materials And Methods: TLR9 expression was analyzed by real-time polymerase chain reaction (PCR) and flow cytometry in 35 SLE patients and 38 healthy controls and IFN-α concentration was measured in supernatants using enzyme-linked immunosorbent assay (ELISA).

Results: The results showed that the TLR9 expression in the mRNA and the protein level was significantly higher in PBMCs from SLE patients. However, IFN-α concentration in patients and controls significantly increased in response to CpG stimulation but this increase was significantly higher in healthy controls compared with SLE patients. Our results do not show any association between taking hydroxychloroquine and reduction in IFN-α production in SLE patients.

Discussion And Conclusions: Regarding the findings of the study, there is the possibility that TLR9 has played a role in SLE pathogenesis, and consequently it implies that TLRs can be considered to be the therapeutic targets for systemic autoimmunity. We may conclude that PBMCs in patients are functionally impaired in response to TLR ligation via innate response stimulating pathogen-associated molecular patterns (PAMPs).
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http://dx.doi.org/10.1080/08923973.2016.1263859DOI Listing
February 2017

Evaluation of PBMC Distribution and TLR9 Expression in Patients with Systemic Lupus Erythematosus.

Iran J Allergy Asthma Immunol 2016 Jun;15(3):229-36

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which results in damage to various organs. Some animal studies have revealed that activation of Toll-like receptors (TLRs) is important in the pathogenesis of SLE. In the present study, the percentage of different immune cell subsets in 35 SLE patients and 38 control subjects was analyzed by flow cytometry. We also assessed the expression of TLR9 in the population of peripheral blood mononuclear cells (PBMCs) including T lymphocytes (CD4+ and CD8+), B lymphocytes (CD19+), NK cells (CD56+) and monocytes (CD14+) in SLE patients and healthy controls. The results showed that the percentage of CD8+ T lymphocytes and CD14+ monocytes were significantly higher (p˂0.001) in the SLE patients than the healthy control subjects. Moreover, the percentage of CD56+ NK cells were significantly lower in the SLE patients than the healthy control subjects (p=0.001). The findings indicated that the expression of TLR9 was significantly higher in CD4+ and CD8+ T lymphocytes and CD19+ B lymphocytes of SLE patients than in control subjects (all p˂0.05). The difference in TLR9 expression are involved in pathogenesis of the SLE, hence it can be used as an indicator for SLE diagnosis.
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June 2016

Identification, Isolation, and Functional Assay of Regulatory T Cells.

Immunol Invest 2016 Oct 15;45(7):584-602. Epub 2016 Jul 15.

a Department of Immunology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.

Two categories of regulatory T cells (Tregs), nTreg and iTreg, play vital roles in orchestrating the integrity of a host in the course of an immune response. Tregs commonly belong to CD4+ CD25+ T cells and they are characterized by a transcription factor - forkhead box P3 (FoxP3). Within the space of the last few years, interests have been drawn to Tregs as a therapeutic tool in several settings like autoimmune disease, transplantation, and tumor disorders. As a consequence, to assess the functional properties of Tregs, namely through their ability to suppress other cells, cytokine expression, and proliferation in a variety of conditions, it is mandatory to gain better approaches to this end. This would be beneficial in designing better-than-ever therapeutic methods with regard to Tregs properties. Gaining better insights into the underlying mechanisms of immune regulation, by means of straightforward and less time-consuming techniques, will hopefully permit the therapeutic application of these cells in the control of human disorders. This review aims at going through the basic methods for Treg isolation as well the efficiency of the commonly exerted in vitro assays of Tregs-mediated immune suppression.
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http://dx.doi.org/10.1080/08820139.2016.1193869DOI Listing
October 2016

Retinyl Palmitate Supplementation Modulates T-bet and Interferon Gamma Gene Expression in Multiple Sclerosis Patients.

J Mol Neurosci 2016 Jul 28;59(3):360-5. Epub 2016 Apr 28.

Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Vitamin A derivatives such as retinoic acid may improve the impaired balance of CD4+ T cells in autoimmune and inflammatory diseases. This study is a double-blind randomized trial to evaluate the effect of vitamin A (as form of retinyl palmitate) supplementation on multiple sclerosis (MS) patients. Thirty-nine patients were enrolled and randomly assigned to two groups. Both groups were followed for 6 months. The experimental group received 25,000 IU of retinyl palmitate daily, while the control group received a placebo. Before and after the study, the expression of interferon gamma (IFN-γ) and T-bet genes was evaluated in peripheral blood mononuclear cells of patients by RT-PCR. The results showed that after 6 months of supplementation, expression of IFN-γ and T-bet was significantly decreased. These data suggest that retinyl palmitate supplementation can modulate the impaired balance of Th1 and Th2 cells and vitamin A products that may be involved in the therapeutic mechanism of vitamin A in MS patients. This study provides information regarding the decreased gene expression of IFN-γ and T-bet in MS by retinyl palmitate supplementation.
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http://dx.doi.org/10.1007/s12031-016-0747-2DOI Listing
July 2016

Comparison of TGF-β1 and NO production by mesenchymal stem cells isolated from murine lung and adipose tissues.

Immunopharmacol Immunotoxicol 2016 Jun 21;38(3):214-20. Epub 2016 Apr 21.

a Immunoregulation Research Center, Shahed University , Tehran , Iran ;

Context: Mesenchymal stem cells (MSCs) are cell sources for tissues regeneration. By secretion of soluble factors including transforming growth factor-β (TGF-β1) and nitric oxide (NO), MSCs are also able to regulate the immune system. MSCs have been disclosed in lung and adipose tissues with insufficient comparison between the tissues.

Objectives: In this study, specific differentiation and the expression of surface antigens as well as TGF-β1 and NO productive levels were compared in murine lung-derived MSCs (LMSCs) and adipose tissue-derived MSCs (ADMSCs).

Materials And Methods: MSCs were isolated from murine lung and adipose tissues and cultured. Both cell populations were characterized using multilineage potential and the expression of surface antigenic proteins, CD73, CD105, CD34, CD45, and CD11b. Finally, levels of TGF-β1 and NO were evaluated and compared in ADMSCs and LMSCs.

Results: Expression of CD73 and CD105; lack of the expression of CD34, CD45, and CD11b markers; as well as adipocyte and osteocyte differentiations were detected in both adult stem cells. No significant difference was found in TGF-β1 and NO production between two stem cell populations.

Conclusion: Our data showed that LMSCs and ADMSCs have comparable phenotype and TGF-β1 and NO production.
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http://dx.doi.org/10.3109/08923973.2016.1168434DOI Listing
June 2016

Hind limb perconditioning renoprotection by modulation of inflammatory cytokines after renal ischemia/reperfusion.

Ren Fail 2016 Jun 16;38(5):655-62. Epub 2016 Mar 16.

c Department of Immunology, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.

Purpose Renal ischemia/reperfusion (I/R) injury is a common clinical problem associated with significant mortality and morbidity. One newly described strategy to reduce this damage is remote perconditioning (RPEC), in which short-time ischemia of a limb during renal ischemia reduces the I/R-induced kidney injury. This study aimed to assess whether RPEC confer protection through changes in pro-inflammatory mediators. Methods Rats were subjected to right nephrectomy and randomized into: sham (no intervention), I/R (subjected to 45-min left renal ischemia) and RPEC group (subjected to four cycles of 5-min I/R of the femoral artery administered during renal ischemia). After 24-h, blood, urine, and kidney samples were collected. Biochemical indicators of renal dysfunction were measured in the cases of Neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl-B-diglucosaminidase (NAG) activity. Inflammatory cytokines [interleukin (IL)-6 and tumor necrosis factor-alpha, TNF-α] expression in the renal tissues as well as Periodic acid-Schiff stained histological sections were evaluated. Results I/R resulted in renal dysfunction, as evidenced by higher renal NGAL expression and urinary NAG activities. This was accompanied by increased TNF-α and IL-6 expressions as well as histological changes in this group. However, RPEC improved renal histology and function compared with the I/R group. Furthermore, the RPEC group showed decreases in TNF-α and IL-6 expression. Conclusions These results suggest that RPEC reduces the dysfunction and injury associated with I/R of the kidney. This technique reduced the pro-inflammatory cytokine in the kidney. RPEC could be a promising strategy against I/R-induced acute kidney injury partly by down-regulation of inflammatory mediators.
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http://dx.doi.org/10.3109/0886022X.2016.1155387DOI Listing
June 2016

Different Doses of Transforming growth factor-β on In vitro Differentiation of Human Naïve CD4+ T Cells to T Helper 17.

Iran J Allergy Asthma Immunol 2015 Dec;14(6):633-7

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

An appropriate differentiation of distinct human CD4+ T cell subset is critical for manipulating these cells for using in immunity related diseases. Despite various attempts to clarify the role of different factors involved in Th17 differentiation, many crucial contradictions yet remained to be optimized. Although it has been shown that the differentiation of in-vitro Th17 cells culture conditions requires the presence of IL-1beta, IL-23, IL-2, IL-21, IL-6 and TGF-β, the optimum amount of TGF-β regulating in vitro human Th17 cell differentiation is still unclear. In the current study, a flow cytometric assay was used to evaluate the effect of different concentrations of TGF-β and a combination of IL-1beta, IL-23, IL-2 without using IL-6 on development of Interleukin (IL)-17-producing T helper (Th17) cells. According to our findings, 0.1 ng/ml of TGF-β significantly increases the expression of IL-17 in comparison to other concentrations of this cytokine. Results indicated the vital role of TGF-β cytokine in the polarization of human Th17 cells in vitro.
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December 2015

The Effect of Vitamin A Supplementation on FoxP3 and TGF-β Gene Expression in Avonex-Treated Multiple Sclerosis Patients.

J Mol Neurosci 2015 Jul 19;56(3):608-12. Epub 2015 May 19.

Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran,

Multiple sclerosis (MS) is an autoinflammatory condition of the central nervous system with impaired T helper (Th)17 and regulatory T cell (Treg) balance that is involved in disease immunopathogenesis. The vitamin A active metabolite, retinoic acid, can re-establish this imbalance through the modulation of gene expression of specific nuclear receptors including Forkhead box P3 (FoxP3). At present, few data exist on the impact of vitamin A supplementation on T cell balance. This study reports the results of a clinical trial, over a 6-month period, of 36 relapsing-remitting MS (RRMS) patients that received vitamin A (25,000 IU retinyl palmitate) or placebo (one capsule of placebo per day). Peripheral blood mononuclear cells were isolated from patients, and the expression of FoxP3 and transforming growth factor (TGF)-β gene expression was measured using real-time PCR at the beginning and end of the study. The results of this study showed that vitamin A upregulated TGF-β and FoxP3 gene expression. Therefore, vitamin A supplementation can be considered as a new approach in MS prevention and treatment.
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http://dx.doi.org/10.1007/s12031-015-0549-yDOI Listing
July 2015

MicroRNAs in rheumatoid arthritis.

Clin Rheumatol 2015 Apr 4;34(4):615-28. Epub 2015 Mar 4.

Immunology Department, School of Medicine, Tehran University of Medical Sciences, Poursina St, Ghods St, Enghelab Ave, Tehran, 1417613151, Iran.

The role of genetic and epigenetic factors in the development of rheumatic diseases has been an interesting field of research over the past decades all around the world. Research on the role of microRNAs (miRNAs) in rheumatoid arthritis (RA) has been active and ongoing, and investigations have attempted to use miRNAs as biomarkers in disease diagnosis, prognosis, and treatment. This review focuses on experimental researches in the field of miRNAs and RA to present the data available up to this date and includes researches searched by keywords "microRNA" and "rheumatoid arthritis" in PubMed from 2008 to January 2015. All references were also searched for related papers. miRNAs are shown to act as proinflammatory or anti-inflammatory agents in diverse cell types, and their role seems to be regulatory in most instances. Researchers have evaluated miRNAs in patients compared to controls or have investigated their role by overexpressing or silencing them. Multiple targets have been identified in vivo, in vitro, or in silico, and the researches still continue to show their efficacy in clinical settings.
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http://dx.doi.org/10.1007/s10067-015-2898-xDOI Listing
April 2015

Comparison of salivary epidermal growth factor levels in patients with gingivitis and advanced periodontitis and healthy subjects.

J Dent (Tehran) 2014 Sep 30;11(5):516-22. Epub 2014 Sep 30.

Prosthodontist, Private Practice, Tehran, Iran.

Objective: Epidermal growth factor (EGF) is a polypeptide molecule, with important functions in epithelial growth and wound repair. It exerts its effects on cells by binding to receptors on the cell surface. The aim of this study was to evaluate and compare salivary EGF levels in patients with gingivitis and advanced periodontitis as well as in healthy controls.

Material And Methods: Unstimulated salivary samples were collected from patients with gingivitis and advanced periodontitis and healthy individuals. The clinical parameters of plaque index (PI), bleeding on probing (BOP), probing pocket depth (PPD) and clinical attachment level (CAL) were measured and recorded using a Williams probe. The enzyme-linked immunosorbent assay (ELISA) was used to determine salivary levels of EGF. One-way ANOVA was used for data analysis.

Results: The mean salivary level of EGF in healthy individuals (99.27) was significantly higher than that in patients with gingivitis (61.53). This value in patients with gingivitis (61.53) was also significantly higher than that in subjects with periodontitis (36.14) (P<0.001).

Conclusion: The reduction in salivary level of EGF in patients with periodontal disease may be related to the pathogenesis of periodontitis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4290770PMC
September 2014

Whether vitamin A supplementation is effective in T-bet and IFN-ɣ gene expression reduction?

Immunol Invest 2015 11;44(2):189-98. Epub 2014 Dec 11.

Division of Cardiology, Department of Internal Medicine, School of Medicine, Iran University of Medical Sciences , Tehran , Iran .

Background: The aim of present study is evaluation of vitamin A supplementation efficacy on IFN-ɣ and T-bet gene expression in atherosclerotic patients.

Methods: Thirty-one patients and 15 healthy controls participated in this study. Healthy control and patients in Vitamin A group received 25 000 IU retinyl palmitate daily for 4 months. Control patients also received 1 pearl of placebo per day up to 4 months. Gene expression levels were assessed by real-time PCR using SYBR green detection method.

Results: IFN-γ gene expression in fresh cells of patients taking vitamin A declined slightly (0.85-fold, p = 0.068), whereas the expression of this gene was increased in patients taking placebo, and in healthy control subjects 1.2-fold (p = 0.267) and 1.7-fold (p = 0.580), respectively. There were no significant difference (p = 0.159) between 3 groups in terms of IFN-γ gene expression in cells stimulated with PHA. In order to determine whether PHA stimulation of PBMCs in vitro had an effect on T-bet expression, we measured the difference between the 3 groups of studied. The results showed significant differences between the groups (p = 0.046). IFN-γ gene expression in cells activated with ox-LDL in healthy control subjects and patients taking vitamin A, was reduced 0.43 (p = 0.0001) and 0.41 (p = 0.001) respectively, but in placebo patients was increased 2.2-fold (p = 0.959).

Conclusion: Considering role of vitamin A on suppression of Th1 cells in atherosclerotic patients, it can be concluded that vitamin A supplementation may be advantageous for these patients.
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http://dx.doi.org/10.3109/08820139.2014.953635DOI Listing
September 2015

Effects of probiotic yogurt on fat distribution and gene expression of proinflammatory factors in peripheral blood mononuclear cells in overweight and obese people with or without weight-loss diet.

J Am Coll Nutr 2014 31;33(6):417-25. Epub 2014 Jul 31.

a Department of Nutrition, School of Health , Tehran University of Medical Sciences , Tehran , IRAN.

Objectives: The purpose of this study was to investigate whether probiotics had an effect on proinflammatory markers and cytokines in overweight and obese individuals and whether they could have synergistic effects with weight-loss diets.

Methods: A total of 75 healthy overweight and obese individuals completed this randomized doubled-blind controlled clinical trial. Participants were randomly assigned to groups consuming regular yogurt with a low-calorie diet (LCD, RLCD; n = 25) or receiving probiotic yogurt with LCD (PLCD; n = 25) or consuming probiotic yogurt without LCD (PWLCD; n = 25) for 8 weeks. The pribiotic regimen contained 200 g/day yogurt, enriched by Lactobacillus acidophilus La5, Bifidobacterium BB12, and Lactobacillus casei DN001 10(8) colony-forming units/g. Body fat percentage, high-sensitive C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), leptin, and mRNA levels of inflammation-related genes (TNF-α and RAR-related orphan receptor gamma [ROR-γt]) in peripheral blood mononuclear cells (PBMCs) were measured.

Results: A reduction in body mass index (BMI), fat percentage, and leptin level was observed that was more obvious in groups who received the weight-loss diet with probiotic yogurt. Reduction in the gene expression of ROR-γt was significant in the PLCD group (p < 0.001). The expression of TNF-α did not change among all groups after intervention. The mean concentration of leptin was significantly decreased in all groups after the dietary intervention, but the mean changes in leptin level in the PLCD group was more prominent compared to the other two groups (-2.38, p < 0.001 [PLCD] vs -1.75, p = 0.002 [RLCD] and -0.55 ng/mL, p = 0.12 [PWLCD]). The reduction in serum levels of hs-CRP was more evident in the PWLCD group compared to the PLCD and RLCD groups after the 8-week intervention (-3.4, p = 0.03 vs -1.76, p < 0.001 and -2.98 pg/mL, p < 0.001, respectively).

Conclusion: Our results suggested that the weight-loss diet and probiotic yogurt had synergistic effects on T-cells subset specific gene expression in PBMCs, fat percentage, and body weight among overweight and obese individuals.
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http://dx.doi.org/10.1080/07315724.2013.874937DOI Listing
July 2015

The effect of vitamin A supplementation on disease progression, cytokine levels and gene expression in multiple sclerotic patients: study protocol for a randomized controlled trial.

Acta Med Iran 2014 ;52(2):94-100

Department of Cellular and Molecular Nutrition, Faculty of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran. & Food Microbiology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Multiple Sclerosis (MS) is a chronic inflammatory disease that leads to degeneration of the brain and spinal tissue. Imbalances of CD4+ T cells including Thelper1 (Th1)/Thelper2 (Th2) and Thelper17 (Th17)/Tregulatory (Treg), their secreted cytokines and gene expressions, are important aspects of in immunopathogenesis of MS. Vitamin A and its metabolites can regulate the immune system and appears to be effective in preventing progression of the autoimmune disease such as MS. Disease progression was evaluated By Magnetic Resonance Imaging (MRI), Expanded Disability States Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) tests. Cytokine levels were measured using ELISA kits and gene expression was quantified by Real time PCR (RT-PCR) system. According to the difference between the epidemiological and clinical data on the relationship between vitamin A and immune system regulation, this study of the first time assesses Immune function as well as gene expression and progression of the disease following administration of vitamin A supplement.
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November 2014

Effect of estrogen on Th1, Th2 and Th17 cytokines production by proteolipid protein and PHA activated peripheral blood mononuclear cells isolated from multiple sclerosis patients.

Arch Med Res 2014 Feb 28;45(2):177-82. Epub 2014 Jan 28.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Iran. Electronic address:

Background And Aims: A large body of studies has shown that 17-β estradiol (E2) has a protective effect on susceptibility to experimental autoimmune encephalomyelitis (EAE). Clinical improvement in multiple sclerosis and its animal model, EAE, during pregnancy, when estrogen levels are high, suggests an immunomodulatory role for estrogens. The immune basis for this protection is poorly understood. In this study we evaluated the effect of E2 on the synthesis of inflammatory, antiinflammatory and regulatory cytokines.

Methods: We analyzed the effect of E2 on IL-4, IL-10, IL-17, TNF-α and IFN-γ cytokines produced by proteolipid protein (PLP) or mitogen phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells isolated from multiple sclerosis patients in comparison to healthy control group. We used RT-PCR and ELISA to detect the level of cytokines.

Results: We found that E2 significantly increased IL-10 expression and secretion and decreased expression of TNF-α in both groups and IL-4 in patients in cells stimulated with PLP or PHA (p <0.0001).

Conclusion: These data indicated that E2 could affect expression and secretion of inflammatory and anti-inflammatory cytokines and could regulate immune responses especially in the differentiation towards regulatory responses, and this finding might have therapeutic value in multiple sclerosis.
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http://dx.doi.org/10.1016/j.arcmed.2014.01.002DOI Listing
February 2014

The role of interleukin-23 in stability of in vitro T helper-17 cells.

Iran J Allergy Asthma Immunol 2014 Apr;13(2):131-7

Immunology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Interleukin (IL)-17-producing T helper (Th)-17 cells have recently been explained as a distinct population of CD4+ T cells which play an important role in immunity against infectious agents. Establishment of persistent phenotype of Th17 cells and recognition of lineage-deviating factors are of most attractive goals in modern researches in immunology. Although IL-6 and TGF-β are frequently used to differentiate naive T cells to Th17 phenotype in mouse models, the application of IL-23 and its importance in preventing cells from plasticity needs to be more investigated. Our main objective was to evaluate the role of IL-23 in Th17 to Th1 plasticity. In this research project, we generated in vitro Myelin oligodendrocyte glycoprotein (MOG)-specific Th17 cells in the presence of TGF-β, IL-6, IL-23 and peptide MOG35-55. Th17 development was confirmed by assessment of relevant transcription factors and secreted cytokines by flowcytometry and ELISA, respectively. Th17 to Th1 plasticity was monitored by consecutive samplings in different time points without any extra supplementation of IL-23. Cell culture supernatant was evaluated for Interferon (IFN)-γ secretion and cells were evaluated for intracellular expression of this cytokine. Our results showed that the employed method was relatively convenient in developing antigen-specific Th17 cells. We also showed that IL-23 deprivation which happens by prolongation of culture period, can convert IL-17 producing cells to IFN-γ secreting Th1 phenotype. IL-23 can be considered as a Th17 phenotype stabilizing factor for in-vitro developed lineages.
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April 2014

Lactobacillus acidophilus La5, Bifidobacterium BB12, and Lactobacillus casei DN001 modulate gene expression of subset specific transcription factors and cytokines in peripheral blood mononuclear cells of obese and overweight people.

Biofactors 2013 Nov-Dec;39(6):633-43. Epub 2013 Sep 10.

Department of Nutrition, Tehran University of Medical Sciences, Tehran, Iran.

Probiotics are believed to have interaction with immune cells through sustained effects on gene expression of different cytokines and transcription factors. The present randomized doubled-blind controlled clinical trial was performed recruiting 75 individuals with BMI 25-35, who were randomly assigned to the following three groups: Group 1 (n = 25) who consumed regular yogurt as part of a low calorie diet [RLCD], group 2 (n = 25) who received probiotic yogurt with a LCD [PLCD] and group 3 (n = 25) who consumed probiotic yogurt without LCD [PWLCD] for 8 week. Participants in PLCD and PWLCD groups received 200 g/day yogurt containing Lactobacillus acidophilus La5, Bifidobacterium Bb12, and lactobacillus casei DN001 10(8) cfu/gr. The expression of the FOXP3, T-bet, GATA3, TNF-α, IFN-γ, TGF-β, and ROR-γt in PBMCs genes were assessed, before and after intervention. In three groups, ROR-γt expression was reduced (P = 0.007) and FOXP3 was increased (P < 0.001). The expression of TNFα, TGFβ, and GATA3 genes did not change among all groups after intervention. Interestingly, the expression of T-bet gene, which was significantly decreased in PLCD and PWLCD groups (P < 0.001), whereas gene expression of IFN-γ decreased in all three groups. Our results suggest that weight loss diet and probiotic yogurt had synergistic effects on T-cell subset specific gene expression in peripheral blood mononuclear cells among overweight and obese individuals.
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http://dx.doi.org/10.1002/biof.1128DOI Listing
July 2014

Relationship between probiotic consumption and IL-10 and IL-17 secreted by PBMCs in overweight and obese people.

Iran J Allergy Asthma Immunol 2013 Aug 28;12(4):404-6. Epub 2013 Aug 28.

Department of Nutrition, Tehran University of Medical Sciences, Tehran, Iran.

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August 2013

The effect of vitamin A supplementation on retinoic acid-related orphan receptor γt (RORγt) and interleukin-17 (IL-17) gene expression in Avonex-treated multiple sclerotic patients.

J Mol Neurosci 2013 Nov 19;51(3):749-53. Epub 2013 Jul 19.

Cellular and Molecular Nutrition Department, School of Nutritional Sciences and Dietetics, Tehran university of Medical Sciences, Tehran, Iran.

The aim of this study was to investigate the role of vitamin A on RORγt and IL-17 gene expression in multiple sclerotic patients. Patients in the vitamin A group received 25,000 IU retinyl palmitate per day, while patients in the placebo group took one capsule of placebo per day for 6 months. Gene expression was measured by real-time PCR at the first and end of the study. The results of this study show that vitamin A downregulates IL-17 and RORγt gene expression. No changes in gene expression occurred in the placebo group.
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http://dx.doi.org/10.1007/s12031-013-0058-9DOI Listing
November 2013

In vitro effect of human serum and fetal calf serum on CD4+ T cells proliferation in response to myelin oligodendrocyte glycoprotein (MOG) in correlation with RBP/TTR ratio in multiple sclerotic patients.

J Mol Neurosci 2013 Jul 6;50(3):571-6. Epub 2013 Apr 6.

Cellular and Molecular Nutrition Department, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

Myelin oligodendrocyte glycoprotein (MOG) is one of the autoantigens used in evaluation of the CD4(+) T cells proliferation response in multiple sclerotic patients. In cell culture, human serum (HS) is one of the promising substitutions for fetal calf serum (FCS) that can induce different autoreactivity of T cells and fluctuation of autoantibody production from B cells. Because of immunomodulatory function of vitamin A, we examined the effect of HS and FCS on CD4(+) T cells proliferation in response to MOG in correlation with serum retinol-binding protein (RBP)/transthyretin (TTR) ratio, as an indirect way to assess vitamin A status in multiple sclerotic patients. Patients' peripheral blood mononuclear cells were isolated and cultured in the presence of MOG as well as FCS and HS both separately and together. Cell proliferation was evaluated using BrdU kit. Serum RBP and TTR levels were measured by ELISA kit. FCS and HS increase CD4(+) T cell proliferation. RBP/TTR ratio has significant negative correlation with cell proliferation in the presence of MOG, HS, and FCS. HS with FCS provides an appropriate medium for autoreactivity and proliferation of CD4(+) T cells. Vitamin A has a crucial role in regulation of this pathway.
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http://dx.doi.org/10.1007/s12031-013-9999-2DOI Listing
July 2013

Effect of all-transretinoic acid on Th17 and T regulatory cell subsets in patients with ankylosing spondylitis.

J Rheumatol 2013 Apr 1;40(4):476-83. Epub 2013 Mar 1.

Immunology, Asthma and Allergy Research Institute, Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Objective: We compared Th17 and T regulatory cells in patients with ankylosing spondylitis (AS) and in healthy controls. The effect of all-transretinoic acid (ATRA) was studied on cultured CD4+ T cells of patients with AS compared to controls.

Methods: Eighteen patients with AS and 18 age- and sex-matched healthy controls were included. CD4+ T cells were separated and cultured in conditions of anti-CD3 and anti-CD28 stimulation with and without ATRA. Intracellular and secreted cytokines, transcription factors, and gene expression were evaluated after 72 h.

Results: The frequency of CD4+IL-17+ T cells was significantly higher in patients with AS compared to controls, and ATRA could significantly decrease it. The frequency of forkhead box protein 3 (FOXP3)+ retinoic acid-related orphan receptor γt (RORγt) negative T-bet negative CD4+ cells was significantly lower in cases compared to controls. Intracellular and secreted interferon-γ (IFN-γ) was not significantly different between cases and controls. ATRA significantly increased intracellular IFN-γ in cases but not in controls. Tumor necrosis factor-α (TNF-α) secretion was significantly higher and interleukin 10 secretion was significantly lower in culture supernatant of cases compared to controls. ATRA could significantly decrease TNF-α secretion in cases.

Conclusion: Our findings favor a pathogenic role for Th17 cells in AS. Th1 cells did not seem to contribute in the pathogenesis of this disease. The effect of ATRA as an immunomodulator on deviated immune cells was associated with decreased inflammatory markers. This association could be a reason for a clinical trial of ATRA in patients with AS.
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http://dx.doi.org/10.3899/jrheum.121100DOI Listing
April 2013

Increased expression of CD69 antigen on human peripheral blood natural killer cells in patients with allergic rhinitis.

Iran J Allergy Asthma Immunol 2013 Mar;12(1):68-74

Department of Immunology, Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Allergic rhinitis (AR) is an inflammatory disorder of the nasal mucosa with high morbidity and prevalence. Natural killer (NK) cells might have a role in AR. We aimed to evaluate the changes of the markers and receptors on NK cells in AR patients compared to the non-atopic controls.Flow cytometric analysis was used with double staining of the Peripheral Blood Mononuclear Cells (PBMCs) to examine the expression of CD25 and CD69 markers, and NKG2D and NKG2A receptors on NK cells of 20 patients with AR and 20 non-atopic controls. The serum total IgE level was measured by Enzyme-linked Immunosorbent Assay.The expression of CD69 antigen on NK cells in AR patients was significantly higher than that of healthy group (p=0.03). No significant changes were observed between CD25, NKG2D and NKG2A expression on the surface of NK cells from healthy and AR subjects. Our study also showed that there was no significant correlation between the expression of CD69, CD25, NKG2D and NKG2A and level of serum total IgE in AR patients and normal subjects.These results indicated that the expression of CD69 antigen on NK cells of AR patients was increased. The high expression of CD69 on NK cells in AR patients suggested that these cells were activated, probably due to the cytokines secreted from allergen-stimulated T cells and activated monocytes.
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http://dx.doi.org/012.01/ijaai.688874DOI Listing
March 2013

The influence of vitamin A supplementation on Foxp3 and TGF-β gene expression in atherosclerotic patients.

J Nutrigenet Nutrigenomics 2012 26;5(6):314-26. Epub 2013 Jan 26.

Department of Cellular and Molecular Nutrition, School of Nutrition and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.

The aim of this study was to investigate the role of vitamin A in Foxp3 and TGF-β gene expression in atherosclerotic patients. Patients and healthy controls in the vitamin A group received 25,000 IU retinyl palmitate per day, while patients in the placebo group took one capsule of placebo per day for 4 months. Gene expressions of regulatory T cells were studied by real-time PCR. The levels of Foxp3 expression in phytohemagglutinin-activated cells were much higher in the patients who received vitamin A than in placebo-treated patients and healthy controls, while Foxp3 gene expression in oxidized low-density lipoprotein-activated cells showed no significant differences between all groups (p=0.357). A significant difference in the expression level of TGF-β gene in fresh cells was observed between patients and healthy controls (p=0.009). TGF-β gene expression in oxidized low-density lipoprotein-activated cells increased in all groups; however, these changes were not statistically significant (p=0.65); the changes obtained were 2.8-, 2.2- and 3.9-fold in the vitamin A, placebo, and control groups, respectively. Based on suppressing actions of regulatory T cells on effector T cells and findings that show that vitamin A has the effect of increasing expression of regulatory T cells, it can be concluded that supplementation with vitamin A in atherosclerotic patients may be effective in slowing disease progression.
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http://dx.doi.org/10.1159/000341916DOI Listing
September 2013

Prognostic Value of Promoter Hypermethylation of Retinoic Acid Receptor Beta (RARB) and CDKN2 (p16/MTS1) in Prostate Cancer.

Chin J Cancer Res 2011 Dec;23(4):306-11

Department of Radiation Oncology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran;

Objective: The molecular mechanism of prostate cancer is poorly understood. The aim of the study was to investigate the prevalence and prognostic value of promoter hypermethylation of retinoic acid receptor beta (RARB) and p16 among benign prostatic hyperplasia (BPH) and prostate cancer patients.

Methods: In this case-control study, 63 patients were included in three groups; 21 with BPH as the control group, 21 with prostate cancer and good prognostic factors (based on prostate-specific antigen, Gleason score and stage) as good prognosis group, and 21 with prostate cancer and poor prognostic features as poor prognosis group. The prostate biopsy specimen of each individual was examined for hypermethylation of RARB and p16 promoters by methylation specific PCR (MSPCR).

Results: Seven (33.3%) patients with good prognosis and 15 (71.4%) patients with poor prognosis were positive for RARB methylation, which were significantly higher than controls (P<0.0001). p16 promoter methylation was shown in 19.0% and 47.6% patients with good and poor prognosis, respectively. The RARB and p16 promoter methylation in the poor prognosis group was significantly higher than that in the good prognosis group (P =0.02 for RARB and P<0.0001 for p16).

Conclusion: Hypermethylation of RARB and p16 promoters may predict prognosis in prostate cancer.
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http://dx.doi.org/10.1007/s11670-011-0306-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551302PMC
December 2011

Remote preconditioning reduces oxidative stress, downregulates cyclo-oxygenase-2 expression and attenuates ischaemia-reperfusion-induced acute kidney injury.

Clin Exp Pharmacol Physiol 2013 Feb;40(2):97-103

Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Remote preconditioning (rPeC) is a phenomenon by which short-time intermittent ischaemia-reperfusion (I/R) of a remote organ during ischaemia protects other organs from I/R injury (IRI). The aim of the present study was to investigate the protective effect of rPeC on renal IRI in rats. Rats were subjected to right nephrectomy and randomized as into a sham group (no additional intervention), an I/R group (subjected to 45 min left renal pedicle occlusion) and an rPeC group (subjected to four cycles of 5 min I/R of the left femoral artery administered at the beginning of renal ischaemia). After 24 h, blood, urine and tissue samples were collected. Compared with the sham group, I/R resulted in renal dysfunction, as evidenced by significantly lower creatinine clearance (CCr; 0.52 ± 0.06 vs 0.11 ± 0.02 mL/min, respectively) and higher fractional excretion of sodium (FE(Na) ; 0.80 ± 0.07% vs 2.46 ± 0.20%, respectively). This was accompanied by decreased superoxide dismutase (SOD; 6.9 ± 1.7 vs 26.7 ± 2.7 U/g tissue) and catalase (CAT; 20.2 ± 8.8 vs 32.2 ± 8.7 K/g tissue) activity in the I/R group, as well as decreased levels of reduced glutathione (GSH; 21.7 ± 8.1 vs 81.2 ± 20.2 μmol/g tissue) and increased malondialdehyde levels (MDA; 1.2 to 0.1 vs 0.5 ± 0.2 μmol/100 mg), cyclo-oxygenase (COX)-2 expression and histological damage. In the rPeC group, renal histology and function were significantly improved (CCr 0.32 ± 0.02 mL/min; FE(Na) 1.33 ± 0.12%) compared with the I/R group. Furthermore, compared with the I/R group, the rPeC group exhibited increases in SOD and CAT activity (22.8 ± 3.8 U/g tissue and 21.7 ± 8.6 K/g tissue, respectively), increased GSH levels (74.0 ± 4.9) and decreased MDA levels (1.1 ± 0.3 μmol/100 mg) and COX-2 expression. In conclusion, rPeC appears to exert protective effects against renal IRI. This protection may be a consequence of reductions in lipid peroxidation, intensification of anti-oxidant systems and downregulation of COX-2 expression. A simple approach, rPeC may be a promising strategy for protection against IRI in clinical practice.
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http://dx.doi.org/10.1111/1440-1681.12044DOI Listing
February 2013

The in vitro effect of oxidized LDL and PHA on proliferation and gene expression of regulatory T cells in patients with atherosclerosis.

Iran J Allergy Asthma Immunol 2012 Sep;11(3):217-23

Department of Nutrition and Biochemistry, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Atherosclerosis is a chronic inflammatory condition that affects the arterial wall. Oxidized low-density lipoprotein (ox-LDL) seems to have an important role in atherosclerotic plaque formation.This study was performed to investigate the effects of ox-LDL as well as PHA on proliferation and gene expression of peripheral blood mononuclear cells (PBMCs) in patients with atherosclerosis compared to healthy controls. Proliferation of PBMCs was assessed by BrdU assay, while gene expression was assessed by real-time PCR. Both PHA and ox-LDL significantly induced proliferation of PBMCs of patients and controls. PBMCs from controls showed significantly higher proliferation when stimulated with ox-LDL compared to patients. Expression of TGF-β was significantly lower in PBMCs from patients compared to healthy controls (p<0.001). Following simulation with PHA, TGF-β and Foxp3 gene expression levels in patients and controls were significantly decreased (p<0.001). Expression of Foxp3 in PBMCs treated with ox-LDL was significantly decreased in patients and controls.Decreased expression of TGF-β and Foxp3 genes after ox-LDL stimulation may be due to more sensitivity of Treg cells than effector T cells to ox-LDL. Presence of ox-LDL within atheroma could be associated with the diminished population of Treg cells in the atherosclerotic patients.
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http://dx.doi.org/011.03/ijaai.217223DOI Listing
September 2012