The C Allele of rs5743836 Polymorphism in the Human TLR9 Promoter Links IL-6 and TLR9 Up-Regulation and Confers Increased B-Cell Proliferation

被引：34

作者：

Carvalho, Agostinho ^{[1
,2
,3
]}

Osorio, Nuno S. ^{[1
,2
]}

Saraiva, Margarida ^{[1
,2
]}

Cunha, Cristina ^{[1
,2
,3
]}

Almeida, Agostinho J. ^{[1
,2
]}

Teixeira-Coelho, Maria ^{[1
,2
]}

Ludovico, Paula ^{[1
,2
]}

Pedrosa, Jorge ^{[1
,2
]}

Pitzurra, Lucia ^{[3
]}

Aversa, Franco ^{[4
]}

Romani, Luigina ^{[3
]}

Castro, Antonio G. ^{[1
,2
]}

Rodrigues, Fernando ^{[1
,2
]}

机构：

[1] Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Hlth Sci, Braga, Portugal

[2] ICVS 3Bs PT Govt Associate Lab, Braga, Portugal

[3] Univ Perugia, Dept Expt Med & Biochem Sci, Microbiol Sect, I-06100 Perugia, Italy

[4] Univ Perugia, Div Hematol & Clin Immunol, Dept Clin & Expt Med, I-06100 Perugia, Italy

来源：

PLOS ONE | 2011年 / 6卷 / 11期

关键词：

RECEPTOR GENES; SELF-DNA; DISEASE; SUSCEPTIBILITY; ASSOCIATION; HAPLOTYPES; LYMPHOMA; BINDING;

D O I：

10.1371/journal.pone.0028256

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 cellular responses to CpG, including IL-6 production and B-cell proliferation. Our study uncovers a role for the rs5743836 polymorphism in B-cell biology with implications on TLR9-mediated diseases and on the therapeutic usage of TLR9 agonists/antagonists.

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页数：5

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