Lin Zhou

Second Military Medical University, Shanghai, Shanghai, Shanghai Shi, China

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Publications (8)11.1 Total impact

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    ABSTRACT: Oridonin, a pharmacologically safe agent extracted from Isodon Serra, has been shown to possess potent anti-inflammatory properties. However, it is not clear whether Oridonin affects B-cell activating factor (BAFF) expression, thereby exerting beneficial effects in the treatment of BAFF-associated autoimmune diseases such as systemic lupus erythematosus (SLE). Thus, the current study aimed to find the function of Oridonin in regulation of BAFF and amelioration of SLE. In vitro, we explored the effect of Oridonin on BAFF expression and production in mouse macrophages. Moreover, using a spontaneous murine SLE model, we investigated the role of Oridonin delivery in the treatment of lupus-like disease in MRL(lpr/lpr) mice, by measuring the changes in lupus symptoms, renal damage, BAFF expression, and B cell subsets. Our results showed that Oridonin significantly inhibited BAFF expression in mouse macrophages by suppressing the transcriptional activation of its promoter. And in vivo administration of Oridonin efficiently ameliorated the serological and clinical manifestations of SLE in MRL(lpr/lpr) mice, as shown by increased survival benefit, reduced proteinuria levels, diminished production of specific auto-antibodies, and attenuated renal damage, in association with down-regulation of BAFF and a lower rate of B-cell maturation and differentiation. Thus, it suggests that Oridonin will serve as a novel natural therapeutic strategy for SLE by inhibition of BAFF.
    European journal of pharmacology 05/2013; · 2.59 Impact Factor
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    ABSTRACT: We have previously reported the anti-inflammatory potential and the possible underlying mechanisms of Withangulatin A (WA), which is an active component isolated from Physalis angulata L. Here, we demonstrated that WA might improve the life quality, as well as reduced the accumulation of proteinuria symptoms and levels of anti-double-stranded DNA antibodies in MRL/lpr mice. Moreover, WA could improve renal histopathologic characteristics of MRL/lpr mice. Intriguingly, expression of B cell-activating factor (BAFF), BAFF-R and related gene in the spleen were significantly reduced in 10 mg/kg WA-treated mice compared with that in 5 mg/kg WA-treated mice and untreated mice. These findings indicate that WA might have a pleiotropic therapeutic effect through their immunosuppression via inhibiting BAFF signaling, which suggest a potential application of this active constituent in the treatment of SLE.
    Journal of Cellular Biochemistry 04/2011; 112(9):2376-82. · 3.06 Impact Factor
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    ABSTRACT: B-cell activating factor (BAFF) is a potent cell-survival factor, expressed in many hematopoietic cells, for B-cell maturation and activation. It is involved in pathogenesis of autoimmune disorders and B-cell malignancies. Although BAFF is produced by interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) in monocytes, the mechanisms of the modulation of BAFF production and expression under normal and pathologic conditions have not been completely elucidated. In this study, we examined the effects of several inflammatory cytokines on BAFF expression in cultured human promyelocytic leukemia (HL-60) cells both at the transcriptional and posttranscriptional level. Incubation of the cells with IL-10 and IFN-gamma elevated the expression of membrane-bound and soluble forms of BAFF. A similar increase in BAFF-specific mRNA was noted in cultured cells. Unexpectedly, interleukin-4 (IL-4) treatment hardly affected BAFF expression at the mRNA and protein levels. Transcriptional regulation was examined in cultures transfected with a human BAFF promoter/reporter gene (chloramphenicol acetyltransferase) construct. IL-10 and IFN-gamma elicited marked enhancement of the human BAFF promoter activity. Collectively, these results demonstrated that IL-10 and IFN-gamma both regulate BAFF expression and synthesis in human promyelocytic leukemia cell cultures, and the activation occurs at the transcriptional level.
    Experimental and Molecular Pathology 05/2009; 87(1):54-8. · 2.13 Impact Factor
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    ABSTRACT: To quantitate antigen specific T lymphocytes in peripheral blood from patients with primary biliary cirrhosis(PBC) and study the role of antigen specific T lymphocytes in the development of PBC. Using tetramers and CD8 monoclonal antibody staining, PDC-E2 159-167aa and PDC-E2 165-174aa specific CD8(+) T lymphocytes were determined respectively in the peptide-induced cytotoxic T cell lines prepared from peripheral blood mononuclear cells(PBMC) of 15 PBC patients. The frequencies of these two kinds of antigen specific T lymphocytes in HLA-A*0201 positive (A2(+)) PBC were compared with those in A2(-) PBC patients, patients with other A2(+) chronic liver diseases and healthy controls. PDC-E2 159-167aa/HLA-A*0201 and PDC-E2 165-174aa/HLA-A*0201 tetramer positive CD8(+) T lymphocytes were detected in all of A2(+) PBC patients with average percentages of 0.42%+/-0.24% (0.17%-1.08%) and 0.27%+/-0.17% (0.05%-0.56%), respectively. The frequencies of the two kinds of antigen specific CD8(+) T lymphocytes from peripheral blood were significantly higher in earlier stages I and II of PBC as compared with stage III (P<0.001), while no difference was found between PDC-E2 159-167aa and PDC-E2 165-174aa specific CD8(+) T lymphocytes at the same stages. In addition, there existed no statistical difference between frequencies of antigen specific T lymphocytes in AMA or anti-PDC positive and negative PBC patients (P>0.05). This study suggests that HLA-A*0201 restricted PDC-E2 165-174aa and PDC-E2 159-167aa specific CTL play important roles in the development of PBC, and there might be a similar mechanism of T cell-mediated damage between AMA or anti-PDC positive and negative PBC patients.
    Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 01/2006; 22(1):78-81.
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    ABSTRACT: Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are two autoimmune diseases of unknown etiology. Genetic factors appear to be involved in the pathogenesis of both diseases. Vitamin D has been shown to exert multiple immunomodulatory effects, which acts through its own receptor (VDR). Polymorphisms of VDR had been implicated in several autoimmune diseases. In the present study, the association between Chinese patients with AIH, PBC and the polymorphisms in exon 2, intron 8 and exon 9 of vitamin D receptor genes was studied. Four candidate gene loci were investigated in 49 patients with AIH, 58 patients with PBC, and 160 healthy controls. The VDR polymorphisms were assessed by FokI, BsmI, ApaI, and TaqI endonuclease digestion after specific polymerase chain reaction (PCR) amplification. The result show a significant difference in FokI polymorphism between AIH patients and controls (chi(2) = 5.47, P = 0.019), and a significant association in BsmI polymorphisms between PBC patients and controls (chi(2) = 6.52, P = 0.01). Furthermore the distribution of FokI, BsmI, ApaI, and TaqI gene types differed between Chinese healthy controls and Caucasian healthy controls. It is suggested that there is a genetic link of VDR polymorphisms to autoimmune liver diseases such as AIH and PBC in Chinese patients. Further studies are needed to elucidate the mechanisms by which VDR polymorphisms contribute to the lose of immune tolerance in autoimmune diseases.
    Journal of Gastroenterology and Hepatology 03/2005; 20(2):249-55. · 3.33 Impact Factor
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    ABSTRACT: To investigate the association between Chinese patients with autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and the polymorphisms of cytotoxic T lymphocyte -associated antigen-4 (CTLA-4) gene promoter (-318) and exon 1 (+49). The CTLA-4 promoter (-318 T/C) and exon 1 (+49A/G) polymorphisms were genotyped via restriction fragment length polymorphism methods in 62 Chinese AIH patients, 77 Chinese PBC patients and 160 healthy controls. There was no difference in the distribution of CTLA-4 promoter -318 T/C polymorphisms between AIH patients and controls, but the C allele frequency was significantly increased in patients with AIH, compared to controls (P=0.02, OR=2.43). The distribution of CTLA-4 gene exon 1 49 A/G genotypes exhibited significant difference between PBC patients and controls (P=0.006), and the frequency of G allele showed a significant increase in PBC group as compared with controls (P=0.0046, OR=1.8). Although the genotype distribution of the CTLA-4 exon 1-promoter gene displayed no significant difference between AIH and PBC patients and controls, the occurrence of GG-CC was increased in the patients of the two groups (AIH: 32.3%, PBC: 37.7%; control: 22.5%). The above findings suggest that the polymorphisms of CTLA-4 gene probably confer susceptibility to AIH and PBC in the Chinese population.
    Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 11/2004; 21(5):440-3.
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    ABSTRACT: Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are two autoimmune diseases of unknown etiology. Genetic factors appear to be involved in the pathogenesis of both diseases. Tumor necrosis factor (TNF)-alpha is one of the proinflammatory cytokines and immunomodulators, and is implicated in the pathogenesis of AIH and PBC. In this study, we studied the association between Chinese patients with AIH, PBC and the polymorphisms in promoter-region polymorphisms of the TNF-alpha gene at position -308 and -238. We have investigated four candidate gene loci in 49 patients with AIH, 58 patients with PBC, and 160 healthy controls. The polymorphisms were assessed by the PCR specifically for the single-nucleotide polymorphisms. We found the difference in the TNF-alpha gene at position -308 genotype distributions between Chinese health controls and Caucasian health controls. Although the percent of TNF-alpha*2 was decrease on PBC patient group (10.34% vs. 16.88%), there was no significant difference between PBC patients and health control in the Chinese. There were also no significant differences between AIH and health control on the TNF-alpha gene at position -308 and -238. Our findings suggest that the TNF-alpha promoter-region polymorphisms distribution is different between differe of ethnic groups; there are no genetic links of the TNF-alpha promoter-region polymorphisms to AIH and PBC in Chinese.
    Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 04/2004; 12(3):160-2.
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    ABSTRACT: To study the association between the polymorphisms of vitamin D receptor (VDR) gene and autoimmune liver diseases and (AIH) and primary biliary cirrhosis (PBC) in Chinese. PCR-RELP was used to investigate the polymorphisms in exon 2, and exon 7 to exon 9 of VDR among 49 AIH patients, 58 PBC patients, and 160 healthy controls, all Chinese. VDR polymorphisms were assessed by FokI, BsmI, ApaI, and TaqI endonucleases restriction fragment length polymorphism analysis after specific polymerase chain reaction (PCR) amplification. The distribution of VDR gene polymorphism in Chinese was similar to those in Koreans and Japanese, and different from those in the Germans and Spaniards. The percentage of ff phenotype carriers was significantly higher in the AIH patients than in the healthy controls (34.7% vs. 48.1%, chi(2) = 5.47, P = 0.019) and the percentage of Ff phenotype carriers was lower in the AIH patients than in the healthy controls (34.7% vs. 48.1%, P = 0.057). The percentage of Bb phenotype carriers was significantly lower in the PBC patients than in the healthy controls (5.2% vs. 17.5%, P = 0.021) and. the percentage of bb phenotype carriers was significantly higher in the PBC patients than in the healthy controls (94.8% vs. 80.6%, chi(2) = 6.52, P = 0.01). We also detected a significant association of the BsmI polymorphisms in PBC patients in comparison with controls (P = 0.01). Furthermore we found the difference in the FokI, BsmI, ApaI, and TaqI genotype distribution between Chinese health controls and Caucasian health controls. There is a significant association between FokI polymorphism and AIH and a significant association between the BsmI polymorphisms and PBC in Chinese.
    Zhonghua yi xue za zhi 12/2003; 83(21):1852-5.