the c allele of rs5743836 polymorphism in the human tlr9 promoter links il-6 and tlr9 up-regulation and confers increased b-cell proliferationrs5743836 c等位基因的多态性在人类tlr9识别启动子链接il - 6和tlr9识别上调和可以提高b细胞增殖.pdfVIP

The C Allele of rs5743836 Polymorphism in the Human TLR9 Promoter Links IL-6 and TLR9 Up-Regulation and Confers Increased B-Cell Proliferation 1,2,3 ´ 1,2 1,2 1,2,3 Agostinho Carvalho , Nuno S. Osorio , Margarida Saraiva , Cristina Cunha , Agostinho J. 1,2 1,2 1,2 1,2 3 Almeida , Maria Teixeira-Coelho , Paula Ludovico , Jorge Pedrosa , Lucia Pitzurra , Franco 4 3 ´ 1,2. 1,2 . Aversa , Luigina Romani , Antonio G. Castro , Fernando Rodrigues * 1 Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal, 2 ICVS/3B’s - PT Government Associate Laboratory, ˜ Braga/Guimaraes, Portugal, 3 Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy, 4 Division of Hematology and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy Abstract In humans, allelic variants in Toll-like receptors (TLRs) associate with several pathologies. However, the underlying cellular and molecular mechanisms of this association remain largely unknown. Analysis of the human TLR9 promoter revealed that the C allele of the rs5743836 polymorphism generates several regulatory sites, including an IL-6-responding element. Here, we show that, in mononuclear cells carrying the TC genotype of rs5743836, IL-6 up-regulates TLR9 expression, leading to exacerbated