Publications by authors named "Lunxian Tang"

24 Publications

  • Page 1 of 1

Prevalence and related factors of hyperuricaemia in Shanghai adult women of different ages: a multicentre and cross-sectional study.

BMJ Open 2021 Sep 16;11(9):e048405. Epub 2021 Sep 16.

Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

Objective: Women in different age phases have different metabolism and hormone levels that influence the production and excretion of uric acid. We aimed to investigate the prevalence and related factors of hyperuricaemia among women in various age phases.

Study Design: Observational, cross-sectional study.

Setting: Data were obtained from women at three health check-up centres in Shanghai.

Participants: Adult women from three health check-up centres were recruited. Exclusion criteria were individuals with pregnancy, cancer, incomplete information. Finally, 11 601 participants were enrolled.

Results: The prevalence rates of hyperuricaemia of total subjects were 11.15% (95% CIs 10.57% to 11.72%). The prevalence of hyperuricaemia in 18-29, 30-39, 40-49, 50-59, 60-69 and ≥70 years old was 6.41% (95% CI 4.97% to 7.86%), 5.63% (4.71% to 6.55%), 6.02% (5.01%% to 7.03%), 11.51% (10.19% to 12.82%), 16.49% (15.03% to 17.95%) and 23.98% (21.56% to 26.40%), respectively. Compared with 18-29 years old, the ORs for hyperuricaemia in other age phases were 0.870 (95% CI 0.647 to 1.170, p=0.357), 0.935 (0.693 to 1.261, p=0.659), 1.898 (1.444 to 2.493, p<0.001), 2.882 (2.216 to 3.748, p<0.001) and 4.602 (3.497 to 6.056, p<0.001), respectively. During the 18-29 years old, the related factors for hyperuricaemia were obesity and dyslipidaemia. During the 30-59 years old, the related factors were obesity, dyslipidaemia, hypertension and chronic kidney disease (CKD). Over the 60 years old, the occurrence of hyperuricaemia was mainly affected by obesity, dyslipidaemia and CKD, while hypertension cannot be an impact factor for hyperuricaemia independently of obesity and dyslipidaemia.

Conclusion: After 50 years old, the prevalence of hyperuricaemia in Shanghai women has increased significantly and reaches the peak after 70. Obesity and dyslipidaemia are two main related factors for hyperuricaemia during all ages, while diabetes mellitus and nephrolithiasis have no relationship with hyperuricaemia throughout. CKD is an independent impact factor for hyperuricaemia after 30 years old.
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http://dx.doi.org/10.1136/bmjopen-2020-048405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449970PMC
September 2021

Requirement of Histone Deacetylase 6 for Interleukin-6 Induced Epithelial-Mesenchymal Transition, Proliferation, and Migration of Peritoneal Mesothelial Cells.

Front Pharmacol 2021 30;12:722638. Epub 2021 Aug 30.

Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Influenced by microenvironment, human peritoneal mesothelial cells (HPMCs) acquired fibrotic phenotype, which was identified as the protagonist for peritoneal fibrosis. In this study, we examined the role of histone deacetylase 6 (HDAC6) for interleukin-6 (IL-6) induced epithelial-mesenchymal transition (EMT), proliferation, and migration of HPMCs. The role of HDAC6 in IL-6-elicited EMT of HPMCs was tested by morphological observation of light microscope, immunoblotting, and immune-fluorescence assay; and the function of HDAC6 in proliferation and migration of HPMCs was examined by CCK-8 assay, wound healing experiment, and immunoblotting. IL-6 stimulation significantly increased the expression of HDAC6. Treatment with tubastatin A (TA), a highly selective HDAC6 inhibitor, or silencing of HDAC6 with siRNA decreased the expression of HDAC6. Moreover, TA or HDAC6 siRNA suppressed IL-6-induced EMT, as evidenced by decreased expressions of α-SMA, Fibronectin, and collagen I and the preserved expression of E-cadherin in cultured HPMCs. Mechanistically, HDAC6 inhibition suppressed the expression of transforming growth factor β (TGFβ) receptor I (TGFβRI), phosphorylation of Smad3, secretion of connective tissue growth factor (CTGF), and transcription factor Snail. On the other hand, the pharmacological inhibition or genetic target of HDAC6 suppressed HPMCs proliferation, as evidenced by the decreased optical density of CCK-8 and the expressions of PCNA and Cyclin E. The migratory rate of HPMCs also decreased. Mechanistically, HDAC6 inhibition blocked the activation of JAK2 and STAT3. Our study illustrated that IL-6-induced HDAC6 not only regulated IL-6 itself downstream JAK2/STAT3 signaling but also co-activated the TGF-β/Smad3 signaling, leading to the change of the phenotype and mobility of HPMCs. HDAC6 could be a potential therapeutic target for the prevention and treatment of peritoneal fibrosis.
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http://dx.doi.org/10.3389/fphar.2021.722638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435636PMC
August 2021

Blockade of Autophagy Prevents the Development and Progression of Peritoneal Fibrosis.

Front Pharmacol 2021 23;12:724141. Epub 2021 Aug 23.

Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Peritoneal fibrosis (PF) is a major cause of ultrafiltration failure in long-term peritoneal dialysis (PD) patients. Nevertheless, limited measures have been shown to be effective for the prevention and treatment of PF. Some views reveal that activation of autophagy ameliorates PF but others demonstrate that autophagy promotes PF. It is obvious that the role of autophagy in PF is controversial and further studies are needed. Here, we investigated the role of autophagy in rat models of PF and damaged cultured human peritoneal mesothelial cells (HPMCs). Autophagy was highly activated in fibrotic peritoneum from two PF rat models induced by 4.25% peritoneal dialysate fluid (PDF) and 0.1% chlorhexidine gluconate (CG). Blockade of autophagy with 3-MA effectively prevented PF in both models and reversed epithelial to mesenchymal transition (EMT) by down-regulating TGF-β/Smad3 signaling pathway and downstream nuclear transcription factors Slug and Snail. Treatment with 3-MA also inhibited activation of EGFR/ERK1/2 signaling pathway during PF. Moreover, 3-MA prominently decreased STAT3/NF-κB-mediated inflammatory response and macrophage infiltration, and prevented peritoneal angiogenesis through downregulation of β-catenin signal. In addition, TGF-β1 stimulation up-regulated autophagic activity as evidenced by the increased autophagosome . Exposure of HPMCs to TGF-β1 resulted in the induction of EMT and activation of TGF-β/Smad3, EGFR/ERK1/2 signaling pathways. Treatment with 3-MA blocked all these responses. In addition, delayed administration of 3-MA was effective in reducing EMT induced by TGF-β1. Taken together, our study indicated that autophagy might promote PF and 3-MA had anti-fibrosis effect and . These results suggest that autophagy could be a potential target on PF therapy for clinical patients with long-term PD.
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http://dx.doi.org/10.3389/fphar.2021.724141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419262PMC
August 2021

Inhibition of EZH2 prevents acute respiratory distress syndrome (ARDS)-associated pulmonary fibrosis by regulating the macrophage polarization phenotype.

Respir Res 2021 Jul 3;22(1):194. Epub 2021 Jul 3.

Department of Internal Emergency Medicine and Critical Care, Shanghai East Hospital, Tong Ji University, 1800, Yuntai Road, Shanghai, 200120, China.

Background: We recently reported histone methyltransferase enhancer of zeste homolog 2 (EZH2) as a key epigenetic regulator that contributes to the dysfunction of innate immune responses to sepsis and subsequent lung injury by mediating the imbalance of macrophage polarization. However, the role of EZH2 in acute respiratory distress syndrome (ARDS)-associated fibrosis remains poorly understood.

Methods: In this study, we investigated the role and mechanisms of EZH2 in pulmonary fibrosis in a murine model of LPS-induced ARDS and in ex-vivo cultured alveolar macrophages (MH-S) and mouse lung epithelial cell line (MLE-12) by using 3-deazaneplanocin A (3-DZNeP) and EZH2 the small interfering (si) RNA.

Results: We found that treatment with 3-DZNeP significantly ameliorated the LPS-induced direct lung injury and fibroproliferation by blocking EMT through TGF-β1/Smad signaling pathway and regulating shift of macrophage phenotypes. In the ex-vivo polarized alveolar macrophages cells, treatment with EZH2 siRNA or 3-DZNeP suppressed the M1 while promoted the M2 macrophage differentiation through modulating the STAT/SOCS signaling pathway and activating PPAR-γ. Moreover, we identified that blockade of EZH2 with 3-DZNeP suppressed the epithelial to mesenchymal transition (EMT) in co-cultured bronchoalveolar lavage fluid (BALF) and mouse lung epithelial cell line through down-regulation of TGF-β1, TGF-βR1, Smad2 while up-regulation of Smad7 expression.

Conclusions: These results indicate that EZH2 is involved in the pathological process of ARDS-associated pulmonary fibrosis. Targeting EZH2 may be a potential therapeutic strategy to prevent and treat pulmonary fibrosis post ARDS.
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http://dx.doi.org/10.1186/s12931-021-01785-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255011PMC
July 2021

Clinical outcomes, quality of life, and costs evaluation of peritoneal dialysis management models in Shanghai Songjiang District: a multi-center and prospective cohort study.

Ren Fail 2021 Dec;43(1):754-765

Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

The new Family-Community-Hospital (FCH) three-level comprehensive management aimed to improve the efficiency and scale of peritoneal dialysis (PD) to meet the increased population of end-stage renal disease (ESRD). Our study focused on the clinical outcomes, quality of life, and costs evaluation of this model in a multi-center and prospective cohort study. A total of 190 ESRD patients who commenced PD at Shanghai Songjiang District were enrolled. According to different PD management models, patients were divided into the Family-Community-Hospital three-level management model ( = 90) and the conventional all-course central hospital management model ( = 100). The primary outcome was clinical outcomes of PD. The secondary outcomes were health-related quality of life (HRQOL) and medical costs evaluation. Compared to conventional management, community-based FCH management achieved a similar dialysis therapeutic effect, including dropout rate ( = 0.366), peritonitis rate ( = 0.965), patient survival ( = 0.441), and technique survival ( = 0.589). Follow-up data showed that similar levels of the renal and peritoneal functions, serum albumin, cholesterol and triglyceride, PTH, serum calcium, and phosphorus between the two groups (all  > 0.05). HRQOL survey showed that the FCH management model helped to improve the psychological status of PD patients, including social functioning ( = 0.006), role-emotional ( = 0.032), and mental health ( = 0.036). FCH management also reduced the hospitalization ( = 0.009) and outpatient visits ( = 0.001) and saved annual hospitalization costs ( = 0.005), outpatient costs ( = 0.026), and transport costs ( = 0.006). Compared with conventional management, community-based FCH management achieved similar outcomes, improved psychological health, reduced medical budgets, and thus had a good social prospect.
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http://dx.doi.org/10.1080/0886022X.2021.1918164DOI Listing
December 2021

Correlation analysis between expression of histone deacetylase 6 and clinical parameters in IgA nephropathy patients.

Ren Fail 2021 Dec;43(1):684-697

Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Background: It has been demonstrated that histone deacetylase 6 (HDAC6) is involved in various kidney diseases in experimental study. However, correlation between HDAC6 and clinical parameters in IgA nephropathy (IgAN) patients is still unknown.

Methods: A total of 46 human kidney biopsy specimens with IgAN were selected as observation group, specimens of normal renal cortex tissue that was not affected by the tumor from patients with renal carcinoma ( = 7) served as control. We investigated the relationship between HDAC6 and clinical parameters in IgAN.

Results: HDAC6 was highly expressed in human kidney biopsy specimens with IgAN compared with control group, while the number of acetyl histone H3 positive cells were significantly decreased. There was a statistical difference in the indexes of albumin, estimated glomerular filtration rate (eGFR), serum urea, serum creatinine, serum uric acid, β2-microglobulin, cystatin C, cholesterol, high-density lipoprotein, low-density lipoprotein, and HDAC6 positive area among the different Oxford Classification ( < 0.05). The expression of HDAC6 was different in various eGFR levels, the expression of HDAC6 increased with the decreasing of eGFR level, the expression of acetyl histone H3 decreased with the decreasing of eGFR level. In addition, the expression of HDAC6 positively correlated with Masson trichrome positive area, serum urea, serum creatinine, β2 macroglobulin, and cystatin C, while negatively correlated with eGFR and acetyl histone H3. Multivariate linear regression analysis demonstrated that eGFR and cystatin C were independently associated with HDAC6, respectively ( < 0.05).

Conclusions: These results suggested that high level of HDAC6 expression in IgAN is correlated with renal dysfunction.
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http://dx.doi.org/10.1080/0886022X.2021.1914657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079031PMC
December 2021

Lymphocyte expression of EZH2 is associated with mortality and secondary infectious complications in sepsis.

Int Immunopharmacol 2020 Dec 14;89(Pt B):107042. Epub 2020 Oct 14.

Department of Internal Emergency Medicine and Critical Care, Shanghai East Hospital, Tong Ji University, Shanghai 200120, China. Electronic address:

Recent studies have shown that epigenetic factors may affect immune responses. We previously reported that histone methyltransferase enhancer of zeste homolog 2 (EZH2) was involved in the innate inflammatory responses both in animal model of sepsis and in septic patients. In this study, we prospectively evaluated EZH2 expression kinetics in peripheral CD4+ and CD8+ T cells and HLA-DR expression in CD14+ cells from 48 patients with sepsis and 48 healthy controls. Results showed higher level of EZH2 in CD4+ T cells and CD8+ T cells in sepsis patients than in controls. Meanwhile, EZH2 expression was correlated with CD27 status on T cells. Mean fluorescence intensity (MFI) of EZH2 in CD8+ T cells on day 1 independently predicted death in septic patients. Also, the combination of CD8+ T cell EZH2 expression with APACHEII and SOFA score could enhance the prognostic predictive ability. Moreover, multivariate logistic regression analysis showed that increased expression (proportion and MFI) of EZH2 in CD4+ and CD8+ lymphocytes on day 3 were independently associated with nosocomial infection in septic patients. Additionally, spearman correlation analysis indicated that the levels of EZH2 in CD4+ T cells and CD8+ T cells correlated to CD14+ cells-expressing HLA-DR in patients with sepsis at each time point. Overall, these findings suggest that EZH2 in CD4+ T cells or/and CD8+ T cells may be a novel biomarker for predicting adverse outcomes (mortality and secondary infectious complications) in patients with sepsis.
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http://dx.doi.org/10.1016/j.intimp.2020.107042DOI Listing
December 2020

Blockade of endothelial, but not epithelial, cell expression of PD-L1 following severe shock attenuates the development of indirect acute lung injury in mice.

Am J Physiol Lung Cell Mol Physiol 2020 04 29;318(4):L801-L812. Epub 2020 Jan 29.

Division of Surgical Research, Department of Surgery, Rhode Island Hospital, the Alpert School of Medicine at Brown University, Providence, Rhode Island.

This study sets out to establish the comparative contribution of PD-L1 expression by pulmonary endothelial cells (ECs) and/or epithelial cells (EpiCs) to the development of indirect acute lung injury (iALI) by taking advantage of the observation that treatment with naked siRNA by intratracheal delivery in mice primarily affects lung EpiCs, but not lung ECs, while intravenous delivery of liposomal-encapsulated siRNA largely targets vascular ECs including the lung, but not pulmonary EpiCs. We showed that using a mouse model of iALI [induced by hemorrhagic shock followed by septic challenge (Hem-CLP)], PD-L1 expression on pulmonary ECs or EpiCs was significantly upregulated in the iALI mice at 24 h post-septic insult. After documenting the selective ability of intratracheal versus intravenous delivery of PD-L1 siRNA to inhibit PD-L1 expression on EpiCs versus ECs, respectively, we observed that the iALI-induced elevation of cytokine/chemokine levels (in the bronchoalveolar lavage fluid, lung lysates, or plasma), lung myeloperoxidase and caspase-3 activities could largely only be inhibited by intravenous, but not intratracheal, delivery of PD-L1 siRNA. Moreover, intravenous, but not intratracheal, delivery led to a preservation of normal tissue architecture, lessened pulmonary edema, and reduced neutrophils influx induced by iALI. In addition, in vitro mouse endothelial cell line studies showed that PD-L1 gene knockdown by siRNA or knockout by CRISPR/Cas9-mediated gene manipulation, reduced monolayer permeability, and maintained tight junction protein levels upon recombinant IFN-γ stimulation. Together, these data imply a critical role for pulmonary vascular ECs in mediating PD-1:PD-L1-driven pathological changes resulting from systemic stimuli such as Hem-CLP.
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http://dx.doi.org/10.1152/ajplung.00108.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191484PMC
April 2020

Novel pharmacological inhibition of EZH2 attenuates septic shock by altering innate inflammatory responses to sepsis.

Int Immunopharmacol 2019 Nov 10;76:105899. Epub 2019 Sep 10.

Department of Internal Emergency Medicine and Critical Care, Shanghai East Hospital, Tong Ji University, Shanghai 200120, China; Department of Internal Emergency Medicine and Critical Care, ji'an Hospital, Shanghai East Hospital, ji'an, jiangxi, China. Electronic address:

The function of histone methyltransferase enhancer of zeste homolog 2 (EZH2) in sepsis remains unknown. We reported here that the expression of EZH2 and H3K27me3 was significantly upregulated in the circulation of septic patients, whereas patients who survived presented downregulated the expression of EZH2 on CD14+ monocytes. We further identified increased expression of EZH2 in the circulation, peritoneal fluid, and septic lungs from CLP mice. 3-DZNeP treated CLP mice improved mortality and protected from organ injury. EZH2 inhibition not only suppressed the activation of inflammatory cells and release of cytokines in the circulation and infectious sites, but also promoted bacteria clearance and replenished the circulating monocyte and neutrophil pool from bone marrow. Blockage of EZH2 also suppressed the progression of lung injury and alleviated inflammation by decreasing the pulmonary cell apoptosis, reducing inflammatory cells infiltration and cytokines release through inhibition of the STAT3 signaling pathway and recovery of PPARγ activation. In addition, EZH2 inhibitor blunted macrophage M1 polarization by SOCS3/STAT1 pathway. Overall, these data suggest that EZH2 could be a potential biomarker predicting clinical outcome and a new target for therapeutic interference in sepsis.
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http://dx.doi.org/10.1016/j.intimp.2019.105899DOI Listing
November 2019

Characteristics of circular RNA expression of pulmonary macrophages in mice with sepsis-induced acute lung injury.

J Cell Mol Med 2019 10 14;23(10):7111-7115. Epub 2019 Aug 14.

Department of Internal Emergency Medicine and Critical Care, Shanghai East Hospital, Tong Ji University, Shanghai, China.

Circular RNAs (circRNAs) make up a large class of non-coding RNAs and play important roles in the pathology of a variety of diseases. However, their roles in pulmonary macrophage polarization after sepsisinduced lung injury is unknown. In this study, mice were divided into two groups: Sham control group and cecal ligation and puncture (CLP)-induced ALI group. Macrophages were isolated from lung homogenates 24 hours after SCLP/CLP. We started with RNA-seq of circRNA changes in macrophages and validated by RT-PCR in the following experiments. A total of 4318 circRNAs were detected in the two groups. Of these, 11 and 126 circRNAs were found to be significantly upregulated and downregulated, respectively, compared to the control (p≤0.05, Fold Change ≥2). Differentially expressed circRNAs with a high foldchange (fold-change >4, P<0.05) were selected for validation by qRT-PCR, 10 of which were verified. Furthermore, the most differentially expressed circRNAs within all the comparisons were annotated in detail with circRNA/miRNA interaction information using miRNA target prediction software. The network of circRNA-miRNA-mRNA was illustrated by cytoscape software. Gene ontology analyses indicated the upregulated circRNAs were involved in the multiple biological functions such as regulation of mitochondrion distribution and Notch binding, while the down-regulated circRNAs mainly involved in the biological process as histone H3K27 methylation. KEGG pathway analysis revealed TGF-beta signaling pathway was related to the upregulated circRNAs. The present study provides a novel insight into the roles of circRNAs in pulmonary macrophage differentiation and polarization post septic lung injury.
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http://dx.doi.org/10.1111/jcmm.14577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787439PMC
October 2019

[Effects of histone methyltransferase inhibitor on the polarization of peritoneal macrophages in septic mice].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2019 Feb;31(2):187-192

Department of Emergency Medicine and Critical Care, East Hospital, Tongji University, Shanghai 200120, China.

Objective: To investigate the effect of histone methyltransferase (EZH2) inhibitor on the polarization of peritoneal macrophages in septic mice.

Methods: Thirty-six healthy male C57BL/6J mice were divided into three groups by random number table method (n = 12): sham operated group (Sham group), sepsis model group (CLP group) and EZH2 inhibitor treatment group (CLP+3-DZNeP group). Sepsis animal model was established by cecum ligation and puncture (CLP); Sham group was challenged only by cecum traction without ligation. 3-Deazaneplanocin A (3-DZNeP) 1 mg/kg was intraperitoneal injected 24 hours before and 1 hour after CLP in CLP+3-DZNeP group. Eight mice in each group were sacrificed at 24 hours after surgery. The levels of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in peritoneal lavatory fluid were detected by high throughput liquid protein chip. The expression levels of inducible nitrogenase (iNOS) and macrophage mannose receptor (CD206) were analyzed by flow cytometry. Mouse peritoneal macrophages were isolated and purified by adherent method, the protein expressions of EZH2, peroxisome proliferator-activated receptorγ (PPARγ) were detected by Western Blot. The remaining 4 mice were sacrificed at 48 hours after surgery, the histopathological changes of lung and kidney tissue were evaluated by hematoxylin-eosin (HE) staining.

Results: Compared with Sham group, the infiltration of inflammatory cells in lung and kidney of the CLP group, the levels of IL-6 and TNF-α in peritoneal lavatory fluid were significant increased [IL-6 (ng/L): 7 794.75±405.56 vs. 78.63±74.09, TNF-α (ng/L): 147.25±25.19 vs. 18.20±5.03, both P < 0.01], the percentage of M1 type macrophages was significantly increased [iNOS F4/80: (13.18±8.80)% vs. (1.57±0.77)%, P < 0.05], and the protein expression of EZH2 was significantly increased (EZH2/GAPDH: 0.84±0.11 vs. 0.11±0.03, P < 0.01), while the protein expression of PPARγ was significantly decreased (PPARγ/GAPDH: 0.09±0.01 vs. 0.27±0.09, P < 0.01). Compared with CLP group, the histopathological changes of lung and kidney in CLP+3-DZNeP group were significantly alleviated, the levels of IL-6 and TNF-α in peritoneal lavatory fluid were significantly decreased [IL-6 (ng/L): 4 207.10±876.60 vs. 7 794.75±405.56, TNF-α (ng/L): 63.00±25.37 vs. 147.25±25.19, both P < 0.01 ], the percentage of M1 type macrophages was significantly decreased [iNOS F4/80: (3.64±0.89)% vs. (13.18±8.80)%, P < 0.05], while the percentage of M2 type macrophages was significantly increased [CD206 F4/80: (17.68±5.63)% vs. (7.60±3.17)%, P < 0.01], the protein expression of EZH2 was significantly decreased (EZH2/GAPDH: 0.53±0.09 vs. 0.84±0.11, P < 0.05), and the protein expression of PPARγ was significantly increased (PPARγ/GAPDH: 0.39±0.14 vs. 0.09±0.01, P < 0.05).

Conclusions: Sepsis induces high expression of EZH2 in peritoneal macrophages, and may induce polarization of M1 type macrophages by inhibiting the expression of PPARγ protein. EZH2 inhibitor 3-DZNeP can lessen the inflammatory cytokines release by inhibiting the M1 type macrophages polarization.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2019.02.013DOI Listing
February 2019

Blockade of ERK1/2 by U0126 alleviates uric acid-induced EMT and tubular cell injury in rats with hyperuricemic nephropathy.

Am J Physiol Renal Physiol 2019 04 16;316(4):F660-F673. Epub 2019 Jan 16.

Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine , Shanghai , China.

Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are serine/threonine kinases and function as regulators of cellular proliferation and differentiation. Recently, we demonstrated that inhibition of ERK1/2 alleviates the development and progression of hyperuricemia nephropathy (HN). However, its potential roles in uric acid-induced tubular epithelial-mesenchymal transition (EMT) and tubular epithelial cell injury are unknown. In this study, we showed that hyperuricemic injury induced EMT as characterized by downregulation of E-cadherin and upregulation of vimentin and Snail1 in a rat model of HN. This was coincident with epithelial cells arrested at the G/M phase of cell cycle, activation of Notch1/Jagged-1 and Wnt/β-catenin signaling pathways, and upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9. Administration of U0126, a selective inhibitor of ERK1/2, blocked all these responses. U0126 was also effective in inhibiting renal tubular cell injury, as shown by decreased expression of lipocalin-2 and kidney injury molecule-1 and active forms of caspase-3. U0126 or ERK1/2 siRNA can inhibit tubular cell EMT and cell apoptosis as characterized with decreased expression of cleaved caspase-3. Moreover, ERK1/2 inhibition suppressed hyperuricemic injury-induced oxidative stress as indicated by decreased malondialdehyde and increased superoxide dismutase. Collectively, ERK1/2 inhibition-elicited renal protection is associated with inhibition of EMT through inactivation of multiple signaling pathways and matrix metalloproteinases, as well as attenuation of renal tubule injury by enhancing cellular resistance to oxidative stress.
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http://dx.doi.org/10.1152/ajprenal.00480.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483027PMC
April 2019

[Roles of macrophage-mediated epithelial mesenchymal transdifferentiation in fibrotic diseases].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2018 Jan;30(1):91-93

Tongji University School of Medicine, Shanghai 200120, China (Zhang QQ); Translational Medicine Research Center, East Hospital, Tongji University, Shanghai Institute of Heart Failure, Shanghai 200120, China (Zhou XH); Department of Emergency Medicine and Critical Care, East Hospital, Tongji University, Shanghai 200120, China (Tang LX). Corresponding author: Tang Lunxian, Email:

Objective: It is reported that fibrotic changes seemed to be associated with poor prognosis in patients with organ dysfunction, unfortunately no effective treatment existed currently. Recent studies have demonstrated that macrophages can interact with epithelial cells to induce epithelial mesenchymal transdifferentiation (EMT) which is thought to play a key role in the pathogenesis of a variety of fibrotic diseases. Therefore, this review will summarize the potential role of macrophages in the molecular mechanisms of EMT-associated fibrosis. We aimed to provide a possible therapeutic approaches for the fibrotic diseases.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2018.01.018DOI Listing
January 2018

Tim-3 Regulates Tregs' Ability to Resolve the Inflammation and Proliferation of Acute Lung Injury by Modulating Macrophages Polarization.

Shock 2018 10;50(4):455-464

Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tong Ji University, Shanghai, China.

We recently reported that CD4CD25 regulatory T cells (Tregs) contributed to the recovery of patients with acute lung injury (ALI) by upregulating T cell immunoglobulin and mucin-domain containing-3 (Tim-3). However, the molecular mechanism by which Tim-3 regulates Tregs' function in the resolution and fibroproliferation after ALI remains unknown. In this study, we adoptively transferred Tim-3Tregs or Tim-3Tregs into lipopolysaccharide -induced ALI mice model. Data demonstrated that Tim-3Tregs not only decreased indices of lung inflammation and injury but also mitigated lung fibrosis after ALI. Furthermore, we observed that the transfer of Tim-3Tregs led to M2-like macrophage differentiation as demonstrated by significantly upregulated levels of M2-associated phenotypic markers as well as downregulated expressions of M1-related markers in both the profibrotic lung tissue and sorted pulmonary monocytes after ALI. In addition, cytokines such as interleukin (IL)-10 and IL-4 were also upregulated in lung tissues after Tim-3Tregs transferring. In vitro experiments further demonstrated that cell-contact cocultures with Tregs lacking Tim-3 presented decreased polarization of M2-like macrophages partially mediated by a decreased expression and function of STAT-3. Therefore, these data demonstrate a previously unrecognized function of Tim-3 on Tregs in their ability to repress the fibroproliferation of ALI by inducing alternative macrophages polarization. Moreover, the data highlight that Tim-3Tregs-mediated induction of M2-like macrophages may be a novel treatment modality with transitional potential.
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http://dx.doi.org/10.1097/SHK.0000000000001070DOI Listing
October 2018

[Evaluation value of the levels of peripheral blood CD20 CD24 CD38 regulatory B cells on the prognosis of elderly patients with sepsis].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2017 Aug;29(8):673-678

Department of Emergency, Shanghai East Hospital of Tongji University, Shanghai 200120, China (Wang CM, Tang LX, Bai JW); Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China (Xu HH, Zhang XM). Corresponding author: Bai Jianwen, Email:

Objective: To explore the predicting value of peripheral blood CD20 CD24 CD38 regulatory B cells (Bregs) on the prognosis of elderly patients with sepsis.

Methods: A prospective study was conducted. Septic patients aged > 65 years old, compliance with diagnostic criteria for Sepsis-3, admitted to emergency and emergency intensive care unit (ICU) of Shanghai East Hospital of Tongji University from April 2016 to February 2017 were enrolled. Procalcitonin (PCT), C-reaction protein (CRP) and lactate (Lac) were routinely measured. According to the worst clinical index value within 24 hours, acute physiology and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score were recorded. The concentrations of peripheral blood CD20 CD24 CD38 Bregs were measured by flow cytometry at 1, 3 and 7 days after diagnosed in elderly patients. All patients with sepsis were followed up for 28 days and then divided into death group and survival group according to 28-day outcome. The difference of clinic data and Bregs were compared between the two groups. The significant different factors of elderly sepsis patients were analyzed by binary logistic regression analysis. The correlation between Bregs level and other indicators was analyzed by Spearman correlation. The receiver operating characteristic curve (ROC) was used to evaluate the prognosis value of Bregs in elderly patients with sepsis.

Results: Fifty-eight patients were enrolled in the study, with 38 male and 20 female; age of (79.91±7.97) years; 32 in sepsis group, 26 in septic shock group; 35 deaths, 28-day mortality rate was 60.3%. APACHE II score and SOFA score in death group exhibited much higher than that in survival group (APACHE II: 18.14±4.52 vs. 14.91±3.56, SOFA: 8.80±4.56 vs. 6.35±3.00, both P < 0.05), the Bregs was significantly decreased at 1, 3 and 7 days in death group [cells/μL: 0.70 (0.20, 1.40) vs. 1.50 (0.70, 2.20), 0.54 (0.20, 1.00) vs. 1.42 (1.10, 2.12), 0.25 (0.10, 0.50) vs. 0.80 (0.50, 1.00), all P < 0.05]. Correlation analysis showed that the concentrations of peripheral blood Bregs at 1 day in elderly patients with sepsis was negatively correlated with APACHE II score (r = -0.351, P = 0.007), and it was not correlated with PCT, CRP, Lac or SOFA score. It was shown by binary logistic regression that Bregs [odds ratio (OR) = 1.865, P = 0.028] and APACHE II score (OR = 0.853, P = 0.026) were independent risk factors for elderly sepsis outcome. It was shown by ROC curve analysis that the prognostic value of the levels of Bregs at 1, 3, 7 days and APACHE II score were higher in the elderly patients with sepsis, and the area under ROC curve (AUC) and 95% confidence interval (95%CI) were 0.842 (0.647-0.954), 0.770 (0.564-0.911), 0.888 (0.703-0.977), 0.855 (0.661-0.961), respectively, all P < 0.01. The 7-day Bregs was most powerful to predict outcome, when the cut-off value was 0.50 cells/μL, the sensitivity was 72.73% and specificity was 86.67%.

Conclusions: The level of peripheral blood CD20 CD24 CD38 Bregs could predict the clinical outcome of elderly patients with sepsis.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2017.08.001DOI Listing
August 2017

M2A and M2C Macrophage Subsets Ameliorate Inflammation and Fibroproliferation in Acute Lung Injury Through Interleukin 10 Pathway.

Shock 2017 07;48(1):119-129

*Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tong Ji University, Shanghai, China †Department of Geriatric Medicine, Shanghai East Hospital, Tongji University, Shanghai, China ‡Medical School, Tongji University, Shanghai, China.

The role of M2 macrophages in the resolution and fibroproliferation of acute lung injury (ALI) is poorly understood. In this study, we investigated the effects of two M2 macrophage subtypes, M2a induced by interleukin (IL)-4/IL-13 and M2c induced by IL-10/transforming growth factor -β, on the pathogenesis of ALI. M2a and M2c were adoptively transferred into lipopolysaccharide-induced ALI mice model. Data showed that Vybrant-labeled macrophages appeared in the lungs of ALI mice. Subsequently, we observed that both subsets significantly reduced lung inflammation and injury including a reduction of neutrophil influx into the lung and an augmentation of apoptosis. Interestingly, M2c macrophages more effectively suppressed indices of lung injury than M2a macrophages. M2c macrophages were also more effective than M2a in reduction of lung fibrosis. In addition, we found that M2c but not M2a macrophages increased IL-10 level in lung tissues of the recipient ALI mice partially mediated by activating the JAK1/STAT3/suppressor of cytokine signaling 3 signaling pathway. After blocking IL-10, these superior effects of M2c over M2a were abolished. These data imply that M2c are more potent than M2a macrophages in protecting against lung injury and subsequent fibrosis due to their ability to produce IL-10. Therefore, reprogramming macrophages to M2c subset may be a novel treatment modality with transitional potential.
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http://dx.doi.org/10.1097/SHK.0000000000000820DOI Listing
July 2017

Anti-CCL21 antibody attenuates infarct size and improves cardiac remodeling after myocardial infarction.

Cell Physiol Biochem 2015 23;37(3):979-90. Epub 2015 Sep 23.

Department of Internal Medicine, Emergency Center, East Hospital, Tongji University School of Medicine, Shanghai, China.

Background/aims: Over-activation of cellular inflammatory effectors adversely affects myocardial function after acute myocardial infarction (AMI). The CC-chemokine CCL21 is, via its receptor CCR7, one of the key regulators of inflammation and immune cell recruitment, participates in various inflammatory disorders, including cardiovascular ones. This study explored the therapeutic effect of an anti-CCL21 antibody in cardiac remodeling after myocardial infarction.

Methods And Results: An animal model of AMI generated by left anterior descending coronary artery ligation in C57BL/6 mice resulted in higher levels of circulating CCL21 and cardiac CCR7. Neutralization of CCL21 by intravenous injection of anti-CCL21 monoclonal antibody reduced infarct size after AMI, decreased serum levels of neutrophil and monocyte chemo attractants post AMI, diminished neutrophil and macrophage recruitment in infarcted myocardium, and suppressed MMP-9 and total collagen content in myocardium. Anti-CCL21 treatment also limited cardiac enlargement and improved left ventricular function.

Conclusions: Our study indicated that CCL21 was involved in cardiac remodeling post infarction and anti-CCL21 strategies might be useful in the treatment of AMI.
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http://dx.doi.org/10.1159/000430224DOI Listing
August 2016

Effects of traditional Chinese medicine Fu Zheng decoction on the immunological function and clinical prognosis of the elderly patients with pneumonia.

Cell Biochem Biophys 2015 Jan;71(1):473-80

Department of Emergency Medicine, Shanghai East Hospital, Tong Ji University, Shanghai, 200120, China.

Pneumonia is one of the most serious infectious diseases for elderly people who have impaired organ functions and are more susceptible to infection. Elderly patients having pneumonia often need long-term hospitalization, leading to declined quality of life, and increase of financial burden to the society and their family. Therefore, studies on novel therapeutic strategies and the clinical prognosis of the pneumonia patients are imperative. In the present study, we found that the Chinese herbal medicine Fu Zheng decoction had great immunomodulatory effects during the recovery period of elderly pneumonia patients. Patients treated with combined treatment of Fu Zheng decoction and antibiotic had a faster decline of temperature and a more significant decrease of C reactive protein and inflammatory factors level, and it is easier for them to cough off phlegm, compared with the antibiotic only treatment. Furthermore, the inflammation absorption and the reduction of NK-cell proportion as well as the inflammatory factors were more remarkable in the patients taken Fu Zheng decoction. Especially, the Fu Zheng decoction treatment could decrease the duration of antibiotic treatment, which may help reduce the side effects of antibiotics. Our study also found that MyD88 might play a role in the immunomodulatory effect of Fu Zheng decoction. Our study provides novel insight for the further development of intravenous injection of Chinese materia medica preparation on the regulation of immune function.
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http://dx.doi.org/10.1007/s12013-014-0227-7DOI Listing
January 2015

CD86 polymorphism affects pneumonia-induced sepsis by decreasing gene expression in monocytes.

Inflammation 2015 Apr;38(2):879-85

Department of Internal Medicine, Emergency Center, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China.

Sepsis, a clinical syndrome occurring in patients following infection or injury, is a leading cause of morbidity and mortality worldwide. CD86 (B7-2) is a costimulatory molecule on antigen-presenting cells and plays critical roles in immune responses. In the current study, we investigated the association of two CD86 polymorphisms, rs1129055G/A and rs17281995G/C, with susceptibility to pneumonia-induced sepsis and examined the effects of these two polymorphisms on gene expression in monocytes. CD86 rs1129055G/A and rs17281995G/C were identified in 192 pneumonia-induced septic patients and 201 healthy controls. Data showed that frequencies of the rs1129055GA and AA genotypes were significantly lower in patients than in controls (odds ratio [OR]=0.57, 95 % confidence interval [CI], 0.35-0.93, p=0.023, and OR=0.40, 95 % CI, 0.23-0.71, p=0.002). Interestingly, the other polymorphism, rs17281995G/C, revealed significantly increased numbers in pneumonia-induced sepsis compared to controls (OR=1.85, 95 % CI, 1.07-3.20, p=0.025). Further analyses about CD86 gene expression revealed that both messenger RNA (mRNA) and protein levels of CD86 were downregulated in monocytes from controls carrying rs17281995GC genotype than those carrying wild-type rs17281995GG genotype (p=0.022 and p=0013). These results suggest that polymorphisms in CD86 gene have diverse effects on the pathogenesis of pneumonia-induced sepsis, in which rs17281995G/C may increase the risk of the disease by interfering gene expression of CD86 in monocytes.
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http://dx.doi.org/10.1007/s10753-014-9997-8DOI Listing
April 2015

Active players in resolution of shock/sepsis induced indirect lung injury: immunomodulatory effects of Tregs and PD-1.

J Leukoc Biol 2014 Nov 31;96(5):809-20. Epub 2014 Jul 31.

Department of Surgery, Division of Surgical Research, Alpert School of Medicine at Brown University/Rhode Island Hospital, Providence, Rhode Island, USA

The immunomodulatory effects of PD-1 and CD4(+)CD25(+) Tregs in the resolution of ALI are still poorly understood. Accordingly, 1 million Tregs were isolated from spleens of WT C57BL/6 or PD-1(-/-) mice (magnetical bead purification and subsequent labeling with/without Vybrant dye) and then AT into mice subjected to Hem shock during their resuscitation period, which were subsequently subjected to CLP/septic challenge (24 h post-Hem) to induce iALI. Initially, we demonstrated that Vybrant-labeled AT Tregs appear in the lungs of iALI mice. Subsequently, we found that AT of WT Tregs induced a significant repression of the indices of lung injury: a reduction of neutrophil influx to the lung tissue and a decrease of lung apoptosis compared with vehicle-treated iALI mice. In addition, these mice had substantially higher concentrations of BALF and lung-tissue IL-10 but significantly decreased levels of lung KC. However, these beneficial effects of the AT of Tregs were lost with the administration of PD-1(-/-) mouse Tregs to the recipient WT mice. ALI was exacerbated in these recipient mice receiving AT PD-1(-/-) Tregs to the same extent as iALI mice that did not receive Tregs. These data imply that Tregs can act directly to modify the innate immune response induced by experimental iALI, and this is mediated, in part, by PD-1. Hence, the manipulation of Tregs may represent a plausible target for treating iALI.
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http://dx.doi.org/10.1189/jlb.4MA1213-647RRDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197571PMC
November 2014

Programmed cell death receptor ligand 1 modulates the regulatory T cells' capacity to repress shock/sepsis-induced indirect acute lung injury by recruiting phosphatase SRC homology region 2 domain-containing phosphatase 1.

Shock 2015 Jan;43(1):47-54

*Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tong Ji University, Shanghai, China; and †Division of Surgical Research, Department of Surgery, The Alpert School of Medicine at Brown University/Rhode Island Hospital, Providence, Rhode Island.

We recently reported that adoptively transferred (AT) exogenous CD4+ CD25+ regulatory T cells (Tregs) to wild-type (WT) mice can directly act to repress shock/sepsis-induced experimental indirect acute lung injury (iALI), and this is mediated in part by programmed cell death receptor 1 (PD-1). In this study, we further determine whether recipient mouse lacking PD-L1, one of the primary ligands for PD-1, contributes to the manipulation of the Tregs' capacity to repress lung injury. To do this, Tregs isolated from the spleen of WT mice were AT into PD-L1 mice subjected to hemorrhagic shock and subsequent to cecal ligation and puncture to induce iALI. Samples were collected for analyses 24 h after cecal ligation and puncture. We found that in PD-L1-recipient mice, AT WT-Tregs lost the ability to reverse the development of iALI seen in WT recipient mice (i.e., no reduction of lung injury indices assessed by histology and vascular leakage, failure to decrease the lung neutrophil influx [myeloperoxidase activity], or the rise in lung apoptosis [caspase 3 activity]). Also, a significant increase in interleukin 1β (IL-1β) and keratinocyte-derived chemokine, but no changes in IL-6, IL-10, and IL-17A levels in lung tissues were seen in these mice compared with iALI mice without AT of Tregs. Furthermore, we noted that the lung tissue tyrosine phosphatase Src homology region 2 domain-containing phosphatase 1 (SHP-1), but not SHP-2, was activated with the AT of Tregs in PD-L1(-/-) iALI mice. Finally, through local depletion of CD4+ T cells or CD25+ (Tregs) in the lung, prior to inducing iALI, we found that SHP-1 activation was associated with the loss of Tregs' protective effects in vivo. Collectively, our data reveal that PD-L1 is a critical modulator of Tregs' ability to suppress iALI, and this appears to involve SHP-1 activation.
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http://dx.doi.org/10.1097/SHK.0000000000000247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269554PMC
January 2015

TAT-SNAP-23 treatment inhibits the priming of neutrophil functions contributing to shock and/or sepsis-induced extra-pulmonary acute lung injury.

Innate Immun 2015 Jan 3;21(1):42-54. Epub 2014 Jan 3.

Department of Surgery, Division of Surgical Research, the Alpert School of Medicine at Brown University/Rhode Island Hospital, Providence, RI, USA

Respiratory burst function of neutrophils is thought to play a pivotal role in the development of pathologies such as indirect (extra-pulmonary) acute lung injury (iALI), as well as sepsis. The current study was conducted to determine the effect of an HIV transactivator of transcription (TAT)-fusion protein containing a soluble N-ethylmaleimide-sensitive factor attachment protein receptor domain from synaptosome-associated protein-23 (SNAP-23) on the shock/sepsis- and sepsis-enhanced neutrophil burst capacity using the clinical relevant two-hit iALI mouse model and the classical cecal ligation and puncture (CLP) septic model. TAT-SNAP-23 significantly decreased the blood neutrophil respiratory burst in vitro, and also in vivo in CLP and hemorrhaged mice. We found that the neutrophil influx to the lung tissue, as measured by myeloperoxidase levels and neutrophil-specific esterase(+) cells, was also decreased in the TAT-SNAP-23-treated group. Consistent with this, treatment of TAT-SNAP-23 significantly reduced the disruption of lung tissue architecture and protein concentration of bronchoalveolar lavage fluid in iALI mice compared with vehicle-treated iALI mice. In addition, although TAT-SNAP-23 did not alter the extent of local cytokine/chemokine expression, the in vitro migration capacity of neutrophils was blunted from septic and hemorrhagic mice. These data support our hypothesis that TAT-SNAP-23 reduces neutrophil dysfunction in iALI and sepsis by inhibiting neutrophil respiratory burst.
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http://dx.doi.org/10.1177/1753425913516524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4092048PMC
January 2015

Expression of cytotoxic T-lymphocyte antigen 4 on CD4+ and CD8+ T cells is increased in acute lung injury.

DNA Cell Biol 2013 Dec 12;32(12):722-6. Epub 2013 Sep 12.

1 School of Occupational Therapy, University of Western Ontario , London, Ontario, Canada .

Acute lung injury (ALI) is a severe form of diffuse lung disease, which imposes a substantial health burden all over the world. The immune system plays a key role in the development of ALI. The aim of the study was to investigate the expression of cytotoxic T-lymphocyte antigen 4 (CTLA4) in ALI. Levels of CTLA4 were tested on CD4+ and CD8+ T cells in 62 ALI cases and 75 healthy controls by flow cytometry. Data revealed that prevalence of CTLA4 on CD4+ T cells was significantly increased in ALI patients (3.7%±2.1%) than in controls (0.7%±0.3%). Similarly, the proportion of CTLA4 on CD8+ T cells was also significantly elevated in cases (1.0%±0.4% versus 0.5%±0.1%, p<0.05). Further analysis showed that the frequency of CTLA4+CD4+ T cells was positively correlated with the score of Acute Physiology and Chronic Health Evaluation II (APACHE II) (p=0.0005). In addition, when investigating CTLA4 expression with ALI patient mortality, we observed that the level of CTLA4+CD4+ T cells in patients was higher at the time before death than at the time of recruitment (p=0.001). These data suggested that CTLA4 was involved in the pathogenesis and progression of ALI and could be used as a potential target for treating this disease.
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http://dx.doi.org/10.1089/dna.2013.2112DOI Listing
December 2013

Severe pneumonia mortality in elderly patients is associated with downregulation of Toll-like receptors 2 and 4 on monocytes.

Am J Med Sci 2014 Jan;347(1):34-41

Department of Central Intensive Care Unit (LT, QL, JB, SM), Geriatric Department (HZ), and The Central Laboratory Department (YL), East Hospital, TongJi University, Shanghai, China.

Background: Elderly patients with pneumonia have a high mortality rate. Since Toll-like receptor (TLR) signaling is involved in the inflammatory response, we conducted a prospective observational case-control study to assess the relationships of TLR2 and TLR4 mortality with elderly patients with pneumonia.

Methods: Clinical and laboratory data were collected from these elderly patients with pneumonia (patient group; n = 40) and healthy age-matched subjects (control 1; n = 20). TLR2 and TLR4 expression levels on blood monocytes were examined, and inflammatory cytokine tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) plasma concentrations were analyzed.

Results: Increased TLR2 and TLR4 expression levels were detected in elderly patients with severe pneumonia compared with healthy subjects. Furthermore, we observed a positive correlation between TLR2 and TLR4 expression levels and IL-1 and IL-6 levels, and TLR2- and TLR4-positive cell percent expressions correlated with TNF-α levels. By day 28 of observation, the mortality rate of the patient group was 30%. Decreased TLR2 and TLR4 expression was observed in deceased patients compared with survivors. APACHE (Acute Physiology and Chronic Health Evaluation) II scores and CURB-65 scores (Confusion, blood Urea nitrogen, Respiratory rate and low Blood pressure scores) were lower in survivors.

Conclusions: These findings demonstrate a previously undocumented association between mortality in elderly patients with severe pneumonia and decreased TLR2 and TLR4 expression. Our results highlight that TLRs can be targeted in the development of improved immune modulation therapies for these patients.
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http://dx.doi.org/10.1097/MAJ.0b013e3182798583DOI Listing
January 2014
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