Peizeng Yang

Xinjiang Medical University, Ouroumtchi, Xinjiang Uygur Zizhiqu, China

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Publications (133)423.81 Total impact

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    ABSTRACT: Purpose: Recent studies have shown that a decrease of regulatory T (Treg) cells may contribute to the activity of acute anterior uveitis (AAU) and ankylosing spondylitis (AS). A number of immunogenetic factors including IL2RA, miR-27a, miR-182 and FoxO1 are associated with Treg cell function. In this study, we investigated the association between polymorphisms of these genes and AAU with or without AS in a Chinese Han population. Methods: Using PCR-RFLP assay, a two-stage association study was performed in 680 AAU patients with or without AS and 1280 controls. Gene expression was quantified by real-time PCR. Results: In the first stage study, an association analysis of 10 single nucleotide polymorphisms (SNPs) was performed in 230 AAU patients with AS, 240 AAU patients without AS and 650 controls. The results showed significantly increased frequencies of the FoxO1/rs2297626 AA genotype and A allele in AAU patients with AS (AA genotype: P =6.23×10-5, OR=1.86; A allele: P =2.17×10-4, OR=1.53). No significant association of the other 9 SNPs with AAU with or without AS was observed. In the second stage study, an association analysis of FoxO1/rs2297626 was performed in 210 AAU patients with AS and 630 controls. The second stage and combined studies confirmed the association of FoxO1/rs2297626 with AAU with AS (AA genotype: P =3.45×10-8, OR=1.85; A allele: P =1.55×10-7, OR=1.55). Conclusions:This study suggests that FoxO1, but not miR-27a, miR-182 and IL2RA, contributes to the genetic susceptibility of AAU with AS, but none of the tested polymorphisms confer risk to AAU without AS.
    Investigative Ophthalmology &amp Visual Science 11/2014; 55(12):7970-7974. · 3.44 Impact Factor
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    ABSTRACT: To investigate the associations of IL17A, IL17F, IL23A, and IL23R copy number variants (CNVs) with Vogt-Koyanagi-Harada (VKH) syndrome and Behçet's disease (BD) and the possible mechanisms involved. Two-stage case-control and functional studies. A total of 1159 VKH patients, 1036 BD patients, and 2050 controls were enrolled. TaqMan real-time polymerase chain reaction assay was used for genotyping of copy number variant. Cell proliferation was measured by colorimetric assay. Association of CNVs in IL17A, IL17F, IL23A, and IL23R with BD and VKH syndrome and the functional roles of IL17F CNVs. Increased frequencies of more than 2 copies of IL17F and IL23A were found in BD patients as compared with controls (IL17F: P = 4.17 × 10(-8); odds ratio [OR], 2.2; IL23A: P = 2.86 × 10(-11); OR, 2.8, respectively). A similar result was found for VKH syndrome (IL17F: P = 2.84 × 10(-13); OR, 2.7; IL23A: P = 4.46 × 10(-17); OR, 3.4, respectively). Interestingly, the association of IL17F and IL23A with BD was found only in male patients (IL17F: P = 1.06 × 10(-6); OR, 2.3; IL23A, P = 3.81 × 10(-8); OR, 2.8, respectively), but not in female patients. No association of CNVs in IL17A and IL23R was found for BD and VKH syndrome. IL17F protein levels were correlated positively with gene copy numbers (P = 3.43 × 10(-7)). Individuals with high IL17F copies showed enhanced peripheral blood mononuclear cells (PBMC) proliferation (P = 5.67 × 10(-3)). High gene copy numbers of IL17F and IL23A were associated with BD and VKH syndrome. Enhanced IL17F protein production and PBMC proliferation were associated with high IL17F copy numbers. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
    Ophthalmology 11/2014; · 5.56 Impact Factor
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    ABSTRACT: Interleukin-37 (IL-37) is emerging as an important inhibitor of immune response. This study was set up to investigate the expression of IL-37 in Vogt-Koyanagi-Harada (VKH) disease and to explore its possible regulatory role during inflammation. Twenty-four untreated active VKH patients, 10 VKH patients receiving corticosteroids and cyclosporin A (CsA), and 35 healthy controls were included in this study. IL-37 expression in lipopolysaccharides (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) from these 3 groups was assayed by real-time polymerase chain reaction (RT-PCR) and flow cytometry. Cytokines in the supernatants of stimulated PBMCs and CD4(+) T cells were assayed by enzyme-linked immunosorbent assay (ELISA). Mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) activation were measured by flow cytometry. VKH patients showed a decreased IL-37 and IL-27 expression and increased IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels in PBMC culture supernatants. IL-37 significantly inhibited the production of IL-1β, IL-6, and TNF-α, but induced IL-27 expression. VKH patients treated with corticosteroids combined with CsA showed a regression of the intraocular inflammation, and treatment was associated with an enhanced IL-37 production. IL-37 did not affect the production of IL-17, interferon-gamma (IFN-γ), or IL-10 from CD4(+) T cells. The present study suggests that a decreased IL-37 expression in VKH patients is associated with a reduced control of the inflammatory response. Treatment of VKH patients with corticosteroids and CsA is associated with an increased expression of IL-37, which suggests that corticosteroids and CsA may partly exert their immunosuppressive effect by upregulating IL-37 production.
    10/2014;
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    ABSTRACT: Considering the phenotypical consequences and association of C4 copy number variation (CNV) with various autoimmune diseases, we aimed to examine C4 CNVs for 1027 patients with Vogt-Koyanagi-Harada (VKH) syndrome and 2083 controls.
    The British journal of ophthalmology. 09/2014;
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    ABSTRACT: To identify new genetic risk factors for Vogt-Koyanagi-Harada (VKH) syndrome, we conducted a genome-wide association study of 2,208,258 SNPs in 774 cases and 2,009 controls with follow-up in a collection of 415 cases and 2,006 controls and a further collection of 349 cases and 1,588 controls from a Han Chinese population. We identified three loci associated with VKH syndrome susceptibility (IL23R-C1orf141, rs117633859, Pcombined = 3.42 × 10(-21), odds ratio (OR) = 1.82; ADO-ZNF365-EGR2, rs442309, Pcombined = 2.97 × 10(-11), OR = 1.37; and HLA-DRB1/DQA1, rs3021304, Pcombined = 1.26 × 10(-118), OR = 2.97). The five non-HLA genes were all expressed in human iris tissue. IL23R was also expressed in the ciliary body, and EGR2 was expressed in the ciliary body and choroid. The risk G allele of rs117633859 in the promoter region of IL23R exhibited low transcriptional activation in a cell-based reporter assay and was associated with diminished IL23R mRNA expression in human peripheral blood mononuclear cells.
    Nature Genetics 08/2014; 46(9):1007-11. · 35.21 Impact Factor
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    ABSTRACT: Instruction: Interleukin (IL)-27 is an important regulator of the pro-inflammatory T cell response. In this study, we investigated its role in the pathogenesis of Behcet's disease (BD).
    Arthritis research & therapy. 05/2014; 16(3):R117.
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    ABSTRACT: Protein tyrosine phosphatase non-receptor 22 (PTPN22) is a key negative regulator of T lymphocytes and has emerged as an important candidate susceptibility factor for a number of immune-related diseases. This study aimed to examine the predisposition of PTPN22 SNPs to Vogt-Koyanagi-Harada (VKH) syndrome and acute anterior uveitis (AAU) associated with ankylosing spondylitis (AS). A total of 1005 VKH syndrome, 302 AAU+AS+ patients and 2010 normal controls among the Chinese Han population were enrolled in the study. Genotyping, PTPN22 expression, cell proliferation, cytokine production and cell activation were examined by PCR-RFLP, Real-time PCR, CCK8, ELISA and Flow cytometry. The results showed significantly increased frequencies of the rs2488457 CC genotype and C allele but a decreased frequency of the GG genotype in VKH syndrome patients (PBonferroni correction (Pc) = 3.47×10-7, OR = 1.54; Pc = 3.83×10-8, OR = 1.40; Pc = 6.35×10-4, OR = 0.62; respectively). No significant association of the tested SNPs with AAU+AS+ patients was observed. Functional studies showed a decreased PTPN22 expression, impaired cell proliferation and lower production of IL-10 in rs2488457 CC cases compared to GG cases (Pc = 0.009, Pc = 0.015 and Pc = 0.048 respectively). No significant association was observed concerning T cell activation and rs2488457 genotype. The study showed that a functional variant of PTPN22 confers risk for VKH syndrome but not for AAU+AS+ in a Chinese Han population, which may be due to a modulation of the PTPN22 expression, PBMC proliferation and IL-10 production.
    PLoS ONE 05/2014; 9(5):e96943. · 3.53 Impact Factor
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    ABSTRACT: Previous studies have identified miR-182, miR-27a, FoxO1, and IL2RA as regulatory factors for Treg cell development and function. In order to investigate the association of miR-182, miR-27a, FoxO1, and IL2RA gene polymorphisms with Behçet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population, a two-stage association study was performed in 820 BD, 900 VKH patients, and 1,800 controls using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. In the first stage study, association analysis of 10 single nucleotide polymorphisms (SNPs) was performed in 400 BD, 400 VKH patients, and 600 controls. The results showed significantly decreased frequencies of the miR-182/rs76481776 CC genotype and C allele in BD (P = 3.36 × 10(-4), OR = 0.55; P = 4.74 × 10(-4), OR = 0.59) and VKH patients (P = 1.11 × 10(-4), OR = 0.53; P = 1.26 × 10(-4), OR = 0.56). No significant association of the other nine SNPs with BD or VKH was observed. In the second stage study, association analysis of miR-182/rs76481776 was performed in 420 BD, 500 VKH patients, and 1,200 controls. The second stage and combined studies confirmed the association of miR-182/rs76481776 with BD (CC genotype: P = 3.25 × 10(-7), OR = 0.58; C allele: P = 1.81 × 10(-7), OR = 0.60) and VKH (CC genotype: P = 7.89 × 10(-8), OR = 0.57; C allele: P = 2.52 × 10(-8), OR = 0.59). Real-time PCR analysis showed a significantly increased expression of miR-182 in TT/CT cases compared to CC cases in anti-CD3/CD28 antibodies-stimulated CD4(+) T cells (P = 2.1 × 10(-2)). In conclusion, this study suggests that miR-182, but not miR-27a, FoxO1, and IL2RA, contributes to the genetic susceptibility of BD and VKH. MiR-182 contributes to genetic susceptibility of BD and VKH. No significant association of miR-27a, FoxO1, and IL2RA with BD or VKH was observed. Significantly increased expression of miR-182 in TT/CT cases compared to CC cases was observed.
    Journal of Molecular Medicine 05/2014; 92(9):961-7. · 4.77 Impact Factor
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    ABSTRACT: Purpose: To investigate whether a synthetic LXR agonist TO901317 (TO90) ameliorates ocular inflammation in experimental autoimmune uveitis (EAU) and to explore its underlying mechanism. Methods: EAU was induced with subcutaneous injection of IRBP161-180 peptide in B10.RIII mice. TO90 were administrated orally for successive 16 or 8 days as prevention or effector phase, respectively. LXRs, p65, ABCA1 and pro-inflammatory genes were detected with real-time PCR and (or) Western blotting. IRBP-specific lymphocyte proliferation was detected by MTT. Intracellular IFN-γ and IL-17 in CD4+T cells were measured by flow cytometry. Results: Both LXRα and LXRβ were expressed in mouse retina. After administrated TO90, the expression of LXRα was upregulated in the naïve mice. It was also increased in vehicle and TO90 treated EAU mice. ABCA1 was enhanced in TO90 treated naïve and EAU mice but was unchanged in vehicle treated EAU mice, suggesting activation of LXRα by TO90 is ligand dependent. Activation of LXRα decreased the expressions of proinflammatory cytokines. TO90 inhibited IRBP-specific immune responses. The proportions of Th1 and Th17 that expressing IFN-γ and IL-17 were reduced in TO90 treated EAU mice in both prevention and effector phases. TO90 significantly down-regulated the expressions of a NF-κB subunit p65. Conclusion: TO90 activates LXRα and potently attenuates ocular inflammation in EAU. Alleviation of ocular inflammation could partially result from inhibition of the NF-κB signaling pathway. TO90 reduces IFN-γ and IL-17 expressing in both prevention and treatment scenarios. Our data suggests that LXR agonist may become a novel class of therapeutic agent for autoimmune uveitis.
    Investigative ophthalmology & visual science 04/2014; · 3.43 Impact Factor
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    ABSTRACT: AhR is well known for mediating the toxic effects of dioxin containing pollutants but has also been shown to be involved in the natural regulation of the immune response. In this study, we investigated the effect of AhR activation by its endogenous ligands 6-formylindolo[3,2-b]carbazole (FICZ), and 2-(1′Hindole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) on the differentiation, maturation and function of monocyte-derived DCs in Behcet's disease (BD) patients. Here, we showed that AhR activation by FICZ and ITE downregulated the expression of co-stimulatory molecules including HLA-DR, CD80 and CD86, while it had no effect on the expression of CD83 and CD40 on DCs derived from BD patients and normal controls. LPS-treated DCs from active BD patients showed a higher level of IL-1β, IL-6, IL-23 and TNF-α production. FICZ or ITE significantly inhibited the production of IL-1β, IL-6, IL-23 and TNF-α, but induced IL-10 production by DCs derived from active BD patients and normal controls. FICZ or ITE-treated DCs significantly inhibited the Th17 and Th1 cell response. Activation of AhR either by FICZ or ITE inhibits DC differentiation, maturation and function. Further studies are needed to investigate whether manipulation of the AhR pathway may be used to treat BD or other autoimmune diseases.
    Clinical & Experimental Immunology 04/2014; · 3.41 Impact Factor
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    ABSTRACT: Objective. Behçet's disease (BD) is a refractory inflammatory disorder with unknown causes. Since the Notch pathway is critically involved in the immune response, the present study was undertaken to investigate the role of this pathway in BD.Methods. Hes-1, Notch 1-4, Jagged-1, DLL-1 and DLL-4 expression, frequency of IFN-γ and IL-17 expressing Th cells, Notch intracellular domain (NICD), phosphorylation of signal transducer and activator of transcription 3 (STAT3) and the production of IFN-γ and IL-17 were examined by real-time PCR, flow cytometry and ELISA. Notch blockade was performed using the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT). Transfection with miR-23b mimics and inhibitor was used to examine the effect of miR-23b on Notch pathway activation.Results. Active BD patients showed an increased activation of the Notch pathway in association with a higher Th17 response. Notch blockade preferentially inhibited Th17 responses. The effect of Notch blockade on the Th17 response was associated with a lower level of STAT3 phosphorylation. miR-23b was significantly decreased in CD4(+) T cells from active BD patients. CD4(+) T cells transfected with miR-23b showed a reduced expression of NICD and a reduced frequency of IL-17- and IFN-γ-expressing T cells.Conclusion. The present study suggests that an increased activation of the Notch pathway may contribute to the pathogenesis of BD. Decreased expression of miR-23b may be involved in activation of the Notch pathway in BD. Manipulation of the Notch pathway may offer a novel therapeutic approach for BD.
    Rheumatology (Oxford, England) 01/2014; 53(5):810-20. · 4.24 Impact Factor
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    ABSTRACT: To investigate the associations of single nucleotide polymorphisms (SNPs) of three genes (IL-12B, IL-12Rβ1 and IL-12Rβ2) in Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population.
    PLoS ONE 01/2014; 9(5):e98373. · 3.53 Impact Factor
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    ABSTRACT: TRAF5 and TRAF3IP2 have been reported to be associated with several autoimmune diseases. Behçet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome are two autoimmune uveitis entities whereby both genetic and environmental factors are thought to be involved. The role of TRAF5 and TRAF3IP2 in BD and VKH has not yet been reported and was therefore the subject of this study. The study included 789 BD patients, 940 VKH patients and 1601 healthy unrelated individuals. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan® SNP Genotyping Assay. Real-Time PCR was used to detect mRNA expression from PBMCs obtained from healthy controls with (n = 22) or without (n = 79) stimulation. Levels of TNF-α, IL-6 and IL-8 in culture supernatants were measured by ELISA (n = 22). Three SNPs (rs6540679, rs12569232, rs10863888) of TRAF5 and rs13210247 of TRAF3IP2 were significantly associated with Behçet's disease and VKH syndrome (corrected P values ranging from 9.45×10(-12) to 0.027). TRAF3IP2 rs33980500 and rs13190932 were not polymorphic in Han Chinese. Following stimulation by lipopolysaccharide (LPS), carriers of the GG genotype of rs6540679/TRAF5 had a higher TRAF5 mRNA expression (p = 0.004) and an increased TNF-α (p = 0.0052) and IL-6 (p = 0.0014) level compared with AA and AG genotype carriers. This study provides evidence that TRAF5 and TRAF3IP2 genes are involved in the development of BD and VKH syndrome. Functional research suggested that TRAF5 gene polymorphisms may regulate TRAF5 expression and downstream inflammatory cytokines such as TNF-α and IL-6.
    PLoS ONE 01/2014; 9(1):e84214. · 3.53 Impact Factor
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    ABSTRACT: MicroRNA-146a (miR-146a) was a key negative regulator of autoimmunity. V-Ets oncogene homolog 1 (Ets-1) was demonstrated to bind to the miR-146a promoter region and markedly affects miR-146a promoter activity. This study aimed to investigate the association of miR-146a and Ets-1 gene polymorphisms with pediatric uveitis in a Han Chinese population. A total of 520 patients and 1204 healthy controls were included in the present study. Five single-nucleotide polymorphisms (SNPs), miR-146a/rs2910164, miR-146a/rs57095329, miR-146a/rs6864584, ets-1/rs1128334 and ets-1/rs10893872 were genotyped using a polymerase chain reaction-restriction fragment length polymorphism assay. The expression of Ets-1 in peripheral blood mononuclear cells from genotyped healthy controls was tested by real-time PCR. Two SNPs (rs2910164 and rs10893872) were associated with pediatric uveitis in this study. The frequencies of the rs2910164 GG genotype and G allele were significantly increased (Pc = 3.11×10-4; Pc = 2.75×10-6) while the CC genotype and C allele were significantly decreased (Pc = 0.001; Pc = 2.75×10-6) in patients compared with normal controls. The frequencies of the rs10893872 CC genotype and C allele were significantly increased (Pc = 3.89×10-4; Pc = 0.01) while the CT genotype and T allele were significantly decreased (Pc = 0.004; Pc = 0.01) in patients compared with normal controls. The SNP rs2910164 GG genotype and G/C allele were also associated with the presence of microvascular leakage as detected by fundus fluorescein angiography in pediatric uveitis (Pc = 0.01; Pc = 0.005, respectively). Ets-1 expression in rs10893872 CC carriers was significantly higher than in CT and TT individuals (Pc = 0.013). There was no association of the other three SNPs with pediatric uveitis. This study shows that miR-146a and Ets-1 are both associated with pediatric uveitis in Han Chinese. SNP rs10893872 may affect the genetic predisposition to pediatric uveitis by modulating expression of Ets-1.
    PLoS ONE 01/2014; 9(3):e91199. · 3.53 Impact Factor
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    ABSTRACT: The aim of the study was to investigate the association of TNFα-induced protein 3 interacting with protein 1 (TNIP1) gene polymorphisms with Vogt-Koyanagi-Harada (VKH) syndrome and Behcet's disease (BD) in a Han Chinese population. A total of 656 BD patients, 961 VKH syndrome patients and 1534 healthy controls were included in this two-stage case control study. Seven SNPs, including rs17728338, rs7708392, rs10036748, rs3762999, rs999556, rs4958881 and rs3792783, belonging to TNIP1 were genotyped and analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The data were analyzed by using the χ2 or Fisher's exact test and corrected for multiple comparisons by the Bonferroni method. A significantly increased frequency of the GG genotype and a decreased frequency of the AG genotype of rs17728338 were found in VKH patients (Pc = 0.038 OR = 1.934, 95% CI = 1.438∼2.601). No significant difference was noted in allele or genotype frequencies of rs7708392, rs10036748, rs3762999, rs999556, rs4958881 and rs3792783, between VKH patients and healthy controls (Pc>0.05). No significant difference was noted in allele or genotype frequencies of the tested 7 SNPs between BD patients and healthy controls. Analysis of extraocular clinical findings, did not reveal an association of the TNIP1 gene polymorphisms with BD or VKH syndrome subgroups. A TNIP1 polymorphism may be a risk factor for VKH syndrome in Han Chinese.
    PLoS ONE 01/2014; 9(5):e95573. · 3.53 Impact Factor
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    ABSTRACT: Recent studies show that the aryl hydrocarbon receptor (AhR) is involved in immune responses. AhR is activated following interaction with its ligands, such as 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). In this study, we investigated the role of AhR activation by its endogenous ligands in the pathogenesis of ocular Behcet's disease (BD). The expression of AhR was significantly decreased in active BD patients as compared to inactive BD patients and normal controls. Both FICZ and ITE inhibited Th1 and Th17 polarization and induced the expression of IL-22 by PBMCs and by CD4(+)T cells in active BD patients and normal controls. Stimulation of purified CD4(+)T cells with FICZ or ITE caused a decreased expression of RORC, IL-17, IL-23R, and CCR6 and an increased phosphorylation of STAT3 and STAT5. The present study suggests that a decreased AhR expression is associated with disease activity in BD patients. The activation of AhR by either FICZ or ITE was able to inhibit Th1 and Th17 cell polarization. Further studies are needed to investigate whether modulation of AhR might be used in the treatment of BD.
    Mediators of Inflammation 01/2014; 2014:195094. · 3.88 Impact Factor
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    Min Sun, Peizeng Yang, Liping Du, Yan Yang, Jian Ye
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    ABSTRACT: To explore whether IRAK1 and IRAK4 are involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. Thirty-nine VKH patients and thirty-two healthy controls were included in this study. The mRNA levels of IRAK1 and IRAK4 from active VKH patients, inactive VKH patients, and normal controls in peripheral blood mononuclear cells (PBMCs) were detected using real-time quantitative PCR. CD4+T cells were purified from PBMCs obtained from active VKH patients and normal controls. The effect of IRAK1/4 inhibition on CD4+T cell proliferation following stimulation with IL-18 or IL-1β was measured using a modified MTT assay. CD4+T cell expression of IFN-γ and IL-17 were detected by flow cytometry (FCM) and enzyme-linked immunosorbent assay (ELISA). The effect of IRAK1/4 inhibition on NF-κB, STAT1, and STAT3 activation was detected by FCM. The mRNA levels of IRAK1 and IRAK4 were both significantly increased in active VKH patients compared to inactive VKH patients and healthy controls. No difference in the IRAK1 or IRAK4 mRNA level could be detected between inactive patients and healthy controls. After incubation with IRAK1/4 inhibitor, the proliferation of CD4+T cells was inhibited both in the active VKH patients and in the healthy controls. IRAK1/4 inhibition was also associated with a decreased expression of IFN-γ and IL-17. Phosphorylation of NF-κB, STAT1, and STAT3 in CD4+T from healthy controls was significantly decreased after inhibition of IRAK1/4. High mRNA levels of IRAK1 and IRAK4 correlated with VKH disease activity. IRAK1 and IRAK4 play a role in the activation and proliferation of CD4+T cells and the higher expression observed in VKH may contribute to the pathogenesis of this blinding condition.
    PLoS ONE 01/2014; 9(4):e93214. · 3.53 Impact Factor
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    ABSTRACT: Abstract Purpose: Vogt-Koyanagi-Harada (VKH) syndrome is a multisystem disorder presumed to be mediated by an autoimmune response. Recent studies have shown that interleukin (IL) 25 was involved in the T-cell immune response. This study analyzed the expression and potential role of IL-25 in the pathogenesis of VKH syndrome. Methods: The IL-25 serum levels were determined by enzyme-linked immunosorbent assay (ELISA). The IL-1β, IL-6, and TNF-α level in supernatants of PBMCs cultured with LPS in the absence or presence of recombinant(r) IL-25 was detected by ELISA. Results: A significantly decreased serum IL-25 level was found in VKH patients. In vitro experiments showed that rIL-25 was able to significantly inhibit the production of IL-1β, IL-6, and TNF-α by PBMCs from active VKH patients. Conclusions: IL-25 may be involved in the development of VKH syndrome, possibly by inhibiting the expression of proinflammatory cytokines.
    Ocular immunology and inflammation 12/2013; · 0.72 Impact Factor
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    ABSTRACT: Purpose: To explore whether SNPs of TLR2, TLR4TLR8 and TLR9 were associated with ocular Behcet's disease, Vogt-Koyanagi-Harada syndrome, acute anterior uveitis with or without ankylosing spondylitis or pediatric uveitis in Han Chinese. Methods: Genotyping was performed by PCR-RFLP. The first stage study comprised 400 ocular BD patients, 400 VKH syndrome patients, 400 AAU ± AS patients, 400 pediatric uveitis patients and 600 healthy subjects. The second stage included 438 ocular BD patients and 1000 healthy subjects. Allele and genotype frequencies were compared between patients and controls using the χ2 test. Real-Time PCR was used to detect mRNA expression from PBMCs obtained from healthy controls. Levels of TNF-α, IL-6, IL-10 and IL-1beta in culture supernatants were measured by ELISA. Results: In the first stage study, only the frequencies of the rs2289318/TLR2 genotype CC and C allele and rs3804099/TLR2 genotype CT were significantly higher in ocular BD patients (pc = 0.048; pc = 0.008; pc = 0.005, respectively) compared with controls. The second stage and combined studies confirmed the association (pc = 0.001; pc = 6.89E-06, pc = 2.426E-06, respectively). TLR2 mRNA expression in PBMCs was increased in healthy carriers of the CC genotype of rs2289318/TLR2 and TT genotype of rs3804099/TLR2 following stimulation with peptidoglycan (PGN) (p=0.028; p = 0.004, respectively). No effect of the various TLR2 rs2289318 and rs3804099 genotypes on the release of TNF-α, IL-6, IL-10 and IL-1beta could be detected. This study provides evidence that the TLR2 gene is involved in the susceptibility to ocular BD.
    Investigative ophthalmology & visual science 11/2013; · 3.43 Impact Factor

Publication Stats

1k Citations
423.81 Total Impact Points

Institutions

  • 2013
    • Xinjiang Medical University
      Ouroumtchi, Xinjiang Uygur Zizhiqu, China
  • 2008–2013
    • Chongqing Medical University
      Ch’ung-ch’ing-shih, Chongqing Shi, China
    • Sun Yat-Sen University Cancer Center
      Shengcheng, Guangdong, China
    • Hui Zhou University
      Cheng, Henan Sheng, China
  • 2012
    • Maastricht Universitair Medisch Centrum
      Maestricht, Limburg, Netherlands
  • 2002–2012
    • Sun Yat-Sen University
      • State Key Laboratory of Oncology
      Guangzhou, Guangdong Sheng, China
    • Zhongshan University
      中山, Guangdong, China
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2011
    • Guangdong Academy of Medical Sciences and General Hospital
      Shengcheng, Guangdong, China
  • 2002–2003
    • Sun Yat-Sen University of Medical Sciences
      中山, Guangdong, China