Liu C.-P.,Soochow University of China |
Jiang J.-A.,Soochow University of China |
Wang T.,Soochow University of China |
Liu X.-M.,Suzhou Health Technology College |
And 6 more authors.
Genetics and Molecular Research
The cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and costimulatory molecule (CD80/CD86) genes are important susceptibility genes associated with autoimmune diseases. CTLA-4 polymorphisms have been found to be associated with various autoimmune diseases. However, the association data are inconsistent for rheumatoid arthritis (RA). We investigated the genetic association of CTLA-4 and CD86 polymorphisms with RA in a Chinese population. Four single nucleotide polymorphisms (SNPs) (rs5742909 and rs231775 in CTLA-4, and rs17281995 and rs1129055 in CD86) were genotyped in 213 patients with RA and 303 healthy controls using polymerase chain reaction-restriction fragment length polymorphism. The genotype and allele distributions of rs5742909 differ significantly between RA patients and controls (P < 0.05) and the dominant model was found to be the best inheritance model. Stratification studies showed that CTLA-4 gene polymorphisms were more significantly associated with rheumatoid factor-negative and anti-cyclic citrullinated peptide-negative subgroups in the southeastern Han Chinese population. We also found that the haplotype of 2 CTLA-4 SNPs showed significant association with the disease (P = 0.0025) with the T-A (OR = 1.88, 95%CI = 1.12-3.15) and T-G (OR = 3.45, 95%CI = 1.10-10.87) haplotypes being observed more frequently in cases than in controls. We failed to find any significant association of the 2 CD86 SNPs with RA. These results indicate that the polymorphisms of CTLA-4 (rs5742909) may be important genetic factors for RA risk in the southeastern Han Chinese population. ©FUNPEC-RP. Source
Sun J.,Suzhou Health Technology College |
Fu F.,Soochow University of China |
Fu F.,Clinical Immunology Laboratory |
Gu W.,Soochow University of China |
And 12 more authors.
B7-H3, a recently identified B7 family member, has different isoforms in human and mouse. Mouse B7-H3 gene has only one isoform (2IgB7-H3) with two Ig-like domains, whereas human B7-H3 has two isoforms (2IgB7-H3 and 4IgB7-H3). In this study a systematic genomic survey across various species from teleost fishes to mammals revealed that 4IgB7-H3 isoform also appeared in pigs, guinea pigs, cows, dogs, African elephants, pandas, megabats and higher primate animals, which resulted from tandem exon duplication. Further sequence analysis indicated that this duplication generated a new conserved region in the first IgC domain, which might disable 4IgB7-H3 from releasing soluble form, while 2IgB7-H3 presented both membrane and soluble forms. Through three-dimensional (3D) structure modeling and fusion-protein binding assays, we discovered that the duplicated isoform had a different structure and might bind to another potential receptor on activated T cells. In T cell proliferation assay, human 2IgB7-H3 (h2IgB7-H3) and mouse B7-H3 (mB7-H3) both increased T cell proliferation and IL-2, IFN-γ production, whereas human 4IgB7-H3 (h4IgB7-H3) reduced cytokine production and T cell proliferation compared to control. Furthermore, both h2IgB7-H3 and mB7-H3 upregulated the function of lipopolysacharide (LPS)-activated monocyte in vitro. Taken together, our data implied that during the evolution of vertebrates, B7-H3 exon duplication contributed to the generation of a new 4IgB7-H3 isoform in many mammalian species, which have carried out distinct functions in the immune responses. © 2011 Sun et al. Source
Gao B.,Soochow University of China |
Chen H.,Soochow University of China |
Shi Z.,Soochow University of China |
Sun J.,Suzhou Health Technology College |
And 3 more authors.
Chinese Journal of Cancer Biotherapy
Objective : To determine the expression and possible roles of miR-29a and B7-H3 in glioma growth and invasion. Methods: Glioma tissue specimens were collected from 19 patients who underwent surgical glioma resection in the Department of Neurosurgery, Soochow University-Affiliated First Hospital between September, 2006 and December, 2010. Levels of miR-29a and B7-H3 mRNAs in the tissue specimens and human glioma U87 cells were determined by Real-time PCR. U87 cells were transfected with miR-29a mimics, and B7-H3 expression and invasive capacity in the transfectants were assessed by flow cytometry and transwell migration assay, respectively. The expression of invasion-related chemical chemokines was analyzed by flow cytometry, and the ability of miR-29a to bind to CXCR4 was predicted by the miRtarbase software. Results: In glioma tissue specimens, miR-29a and B7-H3 mRNA levels were inversely correlated. In vitro, miR-29a down-regulated B7-H3 mRNAs expression in U87 cells and miR-29a-mediated down-regulation of B7-H3 resulted in a significant decrease in the invasive ability but not proliferative activity in U87 cells. Parallel to down-regulation of B7-H3 expression, CXCR4 expression was also down-regulated in U87 cells transfected with miR-29a mimics. No miR-29a binding sites were detected in the CXCR4 gene. Conclusions: In human glioma, miR-29a can effectively down-regulate B7-H3 expression and inhibit invasive activity. It is likely that these effects of miR-29a were at least attributable dwon-regulated expression of CXCR4. © 2015, Editorial office of Chinese Journal of Cancer Biotherapy. All rights reserved. Source