Biomedical subjects

Yongwen Chen

Publications and source records attributed to Yongwen Chen.

9 recordsLinked to original sources

PubMed2007

Terminal complement complex C5b-9-treated human monocyte-derived dendritic cells undergo maturation and induce Th1 polarization.

Sublytic C5b-9 has been described as a pro-inflammatory mediator that triggers cell activation rather than inducing cell death. Dendritic cells (DC) play a critical role in controlling antigen-specific immune responses. Although DC maturation induced by various stimuli has been well characterized, the role of C5b-9 in DC function has not been described. In this report, we use in vitro assembled functional C5b-9 based on purified distal complement protein to show that DC maturation is promoted by sublytic C5b-9. This was demonstrated by up-regulation of CD83, HLA-antigens and costimulatory molecules, including CD80, D86, B7-H1, B7-H3, B7-H4 and BTLA. In addition, secretion of cytokines such as interleukin (IL)-12 and tumor necrosis factor-alpha was increased while the capacity for antigen uptake (FITC-Dextran and Lucifer Yellow) was reduced in C5b-9-treated DC. Mixed lymphocyte reactions indicated that C5b-9-activated DC acted as stimulators that significantly promoted CD4+ T cell activation and elicited production of cytokines, including interferon-gamma and IL-2. Interestingly, C5b-9-treated DC also orient CD4+ CD45RA+ naïve T cells toward Th1 polarization. Our results are the first to report that DC are potential immunoregulatory targets of C5b-9, suggesting that C5b-9 bridges innate and acquired immunity by inducing DC maturation.

Cell Differentiation↗

PubMed2006

Association of polymorphisms in AhR, CYP1A1, GSTM1, and GSTT1 genes with levels of DNA damage in peripheral blood lymphocytes among coke-oven workers.

Accumulating evidence has shown that both DNA damage caused by the metabolites of polycyclic aromatic hydrocarbons (PAH) and genetic polymorphisms in PAH-metabolic genes contribute to individual susceptibility to PAH-induced carcinogenesis. However, the functional relevance of genetic polymorphisms in PAH-metabolic genes in exposed individuals is still unclear. In this study of 240 coke-oven workers (the exposed group) and 123 non-coke-oven workers (the control group), we genotyped for polymorphisms in the AhR, CYP1A1, GSTM1, and GSTT1 genes by PCR methods, and determined the levels of DNA damage in peripheral blood lymphocytes using the alkaline comet assay. We found that the ln-transformed Olive tail moment (Olive TM) values in the exposed group were significantly higher than those in the control group (P < 0.001). Furthermore, in the exposed group, the Olive TM values in subjects with the AhR Lys(554) variant genotype were higher than those with the AhR Arg(554)/Arg(554) genotype (P = 0.021). Similarly, the Olive TM values in the non-coke-oven workers with the CYP1A1 MspI CC + CT genotype were lower than the values of those with the CYP1A1 MspI TT genotype (P = 0.005). However, these differences were not evident for GSTM1 and GSTT1. These results suggested that the polymorphism of AhR might modulate the effects of PAHs in the exposed group; however, the underlying molecular mechanisms by which this polymorphism may have affected the levels of PAH-induced DNA damage warrant further investigation.

Adult↗

PubMed2006

[Association of cadherin CDH23 gene polymorphisms with noise induced hearing loss in Chinese workers].

OBJECTIVE: To investigate the association of cadherin 23 gene (CDH23) polymorphisms with the development of noise induced hearing loss (NIHL). METHODS: 194 workers exposed to occupational noise were drawn as the subjects in the cross-sectional epidemiology study. According to the result of audiometry, they were divided into two groups: the NIHL group and the normal group. The genotypes of 93 workers with NIHL and 101 normal workers were tested by polymerase chain reaction followed by restriction fragment polymorphism analysis (PCR-RFLP). RESULTS: There were no significant difference in the distribution of genotypes and alleles frequencies of the rs1227049 and rs1227051 positions between NIHL group and normal group (P > 0.05), there were significant differences between the two groups in the rs3802711 position and the terminal position of exon 7 (P < 0.01). After adjusted for age, sex, smoking, history of explosive noise exposure and cumulative noise exposure (CNE) with multiple logistic regression analysis, the risk of rs1227049 CC genotype was found significantly increased than that of the GG genotype, the OR value of which was 3.865 (95% CI 1.076 - 13.886), the risk of rs3802711 TT genotype was significantly higher than that of the CT genotype, the OR value of which was 6.088 (95% CI 2.485 - 14.917). GG genotype in the terminal position of exon 7 was also found a significantly higher risk than the AG genotype, the OR value of which was 5.769 (95% CI 2.745 - 12.121). CONCLUSION: It was suggested that genetic polymorphism in cadherin CDH23 gene might play an important role in the development of NIHL in Chinese workers. The individuals with the rs1227049 CC genotype, rs3802711 TT genotype and GG genotype in the terminal position of exon 7 might be more susceptible to NIHL.

Adult↗

PubMed2005

Expression of B7-H1 in inflammatory renal tubular epithelial cells.

BACKGROUND: Renal tubular epithelial cells (TECs) function as antigen-presenting cells (APCs) as they constitutively express MHC-II molecules and have the capacity to present peptide antigen to T cells. Nevertheless, co-stimulatory signals provided by TECs for regulating T cell activation have not been fully characterized. We therefore investigated the expression of B7-H1, a member of the B7 superfamily, on TECs under normal or pathologic conditions in vivo and analyzed the regulation and functional role of it after proinflammatory factors treatment in vitro. METHODS: Immunohistological staining for B7-H1 on cryostat sections of core needle biopsies from patients with different renal diseases was examined. Furthermore, we also detected B7-H1 protein expression on cultured human TECs stimulated by various inflammatory factors and performed TEC/T-cell co-cultured experiment to determine TEC-associated B7-H1 in regulating CD4+ T cell activation as well as antigen presentation. RESULTS: Significant B7-H1 protein was detected in TECs of diseased renal samples. Although the presence of B7-H1 does not have any correlation with clinicopathological variables, marked B7-H1 expression on sections without interstitial inflammation revealed that B7-H1 has some protective function. In vitro, the expression of B7-H1 on TECs was increased after TECs were stimulated with IL-1alpha, LPS, TNF-alpha, IFN-gamma or anti-CD40. Co-cultured experiments revealed that TEC-related B7-H1 was identified as a strong inhibitor of CD4+ T-cell activation as assessed by increased cytokine production (interleukin-2 and interferon-gamma) and expression levels of the T cell activation marker (CD69) in the presence of a neutralizing antibody against B7-H1 (clone MIH1). Interestingly, IL-2 production by C10 T cells after antigen presentation by murine TECs was also enhanced when the B7-H1/PD-1 pathway was interrupted. CONCLUSION: This study clearly shows that B7-H1 is an inducible renal tubular epithelial antigen that inhibits T cell activation. It is speculated that B7-H1/PD-1 pathway might play a role in protecting tubular epithelium from immune-mediated damage and active delivery of the B7-H1 inhibitory signal represents a novel therapeutic strategy in autoimmune renal diseases.

Animals↗

PubMed2005

Triptolide inhibits B7-H1 expression on proinflammatory factor activated renal tubular epithelial cells by decreasing NF-kappaB transcription.

Triptolide has been used extensively in China for the treatment of autoimmune diseases and tumor for many centuries. Nevertheless, little is known about its exact immunosuppressive and anti-inflammatory properties. Increasing recognition of the importance of renal tubular epithelial cells (TECs) in renal diseases raises the question whether triptolide can regulate TEC activity. In this study, various cultured human and murine TECs were exposed to tumor necrotic factor-alpha (TNF-alpha) and triptolide, followed to examine the expression of B7-H1 and B7-DC. Flow cytometric analysis revealed that B7-H1 but not B7-DC constitutively expresses on TECs, and the B7-H1 protein expression was profoundly up-regulated by the stimulation of TNF-alpha with a dose-dependent manner. However, triptolide under non-cytotoxic concentration could down-regulate B7-H1 expression on activated TECs at both mRNA and protein level. This effect was transcription factor NF-kappaB dependent. Interestingly, the significant damping effect of triptolide on B7-H1 signal could promote interleukin-2 production by T cell hybridoma (C10) after antigen presentation and enhance cytokine (IFN-gamma and IL-2) secretion by anti-CD3 activated T cells. Our results indicated that triptolide could regulate TEC activity via B7-H1, in addition to previously reported it directly affects the production of some inflammatory factors by T cells, tumor cells and peripheral blood mononuclear cells.

Animals↗

PubMed2005

Identification of leukemia-associated antigens in chronic myeloid leukemia by proteomic analysis.

The immune system plays an important role in the treatment of chronic myeloid leukemia (CML). Identification of leukemia-associated antigens (LAAs) eliciting an immune response in patients is a prerequisite for specific immunotherapy of CML. To identify new LAAs in CML, We utilized a novel approach based serology and proteomics technologies. LAAs were identified by comparing the reactivity of proteins resolved by 2-DE with sera from CML patients and healthy donors. Several new LAAs were identified including alpha enolase, aldolase A, HSP70 protein8, beta-tubulin and tropomyosin isoforms. Although, the functions of these identified proteins in CML need further investigation, the detection of autoantibodies in CML may have value on CML screening, diagnosis, or follow-up. Additionally, identification of LAAs in CML may also be of vital importance in antigen-based immunotherapy.

Adolescent↗

PubMed2005

Sinomenine inhibits B7-H1 and B7-DC expression on human renal tubular epithelial cells.

Previous studies have shown that sinomenine possesses potent immunoregulatory properties. However, little is known about its exact mechanisms of action. Increasing recognition of the importance of renal tubular epithelial cells (TECs) in renal diseases raises the question whether sinomenine can regulate TEC activity. In this study, cultured human TECs were exposed to proinflammatory factors interferon-gamma (IFN-gamma) and tumor necrotic factor-alpha (TNF-alpha) in presence or absence of sinomenine for 72 h, followed by analysis of surface expression of costimulatory molecules. Flow cytometric analysis revealed that various costimulatory molecules were expressed on TECs and that they were significantly up-regulated by the simulation of IFN-gamma and TNF-alpha. However, sinomenine especially down-regulated B7-H1 and B7-DC expression on TECs at both mRNA and protein levels. Moreover, the significant damping effect of sinomenine on B7-H1 and B7-DC signals could promote IL-2 and IFN-gamma production by co-cultured CD4(+) T cell. Our results indicated that sinomenine could regulate TECs activity via B7-H1 and B7-DC, in addition to previously reported its effects on some pro-inflammatory factors production by macrophages and peripheral blood mononuclear cells.

Antigens, CD↗

PubMed2004

Frequency-specific association of antibodies against heat shock proteins 60 and 70 with noise-induced hearing loss in Chinese workers.

Noise exposure may result in production of auto-antibodies against heat shock proteins (Hsps), which might be of significance in the pathogenesis or prognosis (or both) of auto-immune ear diseases. However, it is not known whether these antibodies are associated with noise-induced hearing loss (NIHL) in workers exposed to noise in occupational settings. Using immunoblotting with human recombinant Hsps, audiological assessment, and multivariate logistic regression models, we investigated the presence of antibodies against Hsp60 and Hsp70 and hearing levels, and analyzed their associations with NIHL in 399 workers exposed to noise between 75 and 115 dB. Our findings showed that the prevalence of positive anti-Hsp70 was significantly higher in the workers with slight and moderate high-frequency hearing loss than in normal workers (P < 0.05). Furthermore, the prevalence of positive anti-Hsp60 in workers with moderate low-frequency NIHL was significantly higher than in the normal (P < 0.01). The levels of anti-Hsp70 and anti-Hsp60 seemed correlated, and the level of anti-Hsp70 better predicted the level of anti-Hsp60. An elevated plasma level of anti-Hsp70 was associated with a nonsignificantly increased risk of high-frequency NIHL (adjusted OR = 1.45; 95% CI = 0.89-2.36) and an elevated plasma level of anti-Hsp60 was associated with a nonsignificantly increased risk of the low-frequency NIHL (adjusted OR = 2.25; 95% CI = 0.85-5.96). These results suggest that the production of anti-Hsp60 and anti-Hsp70 may play a role in the pathogenesis of NIHL, and that anti-Hsps may be a risk factor. The precise mechanisms for the elevation of antibodies against Hsps caused by noise exposure and their possible role in the development of NIHL warrant further investigations.

Adult↗

PubMedDate not supplied

Renal tubular epithelial expression of the coinhibitory molecule B7-DC (programmed death-1 ligand).

BACKGROUND: Renal tubular epithelial cells (TECs) function as antigen-presenting cells because they constitutively express MHC class II molecules and have the ability to present peptide antigen to CD4+T cells. However, the costimulatory signals provided by TECs for optimal T-cell activation have not been fully characterized. Increasing recognition of the importance of B7 dendritic cells (B7-DC) in immunoregulation raises the question of whether B7-DC is expressed on TECs and is involved in regulating TEC function. METHODS: B7-DC on cultured human and murine TECs was detected by flow cytometry in vitro. Immunohistochemistry was performed on human kidney biopsies. Coculture experiments were performed to confirm the role of TEC-related B7-DC in regulating CD4+T-cell activation. RESULTS: Data revealed that B7-DC is specifically expressed on TECs with inflammatory factor induced and diseased human kidney samples, including chronic glomerulonephritis, lupus nephritis, tubulointerstitial nephritis and renal cell carcinoma. B7-DC was a strong inhibitor of CD4+T-cell activation, as assessed by increased cytokine (interferon-gamma and interleukin-2) production and enhanced levels of T-cell activation marker CD69 in the presence of its blocking antibody. Blocking B7-DC/PD-1 enhanced antigen presentation. B7-DC is especially well expressed on TECs of diseased kidney samples and significantly down-regulates T-cell activation. CONCLUSIONS: We speculate that B7-DC might play an important role in maintaining peripheral tolerance, and in protecting the epithelium from immune-mediated tubulointerstitial injury.

Animals↗