Bmx regulates LPS-induced IL-6 and VEGF production via mRNA stability in rheumatoid synovial fibroblasts

被引：23

作者：

Palmer, Christine D. ^{[1
]}

Mutch, Brenda E. ^{[1
]}

Page, Theresa H. ^{[1
]}

Horwood, Nicole J. ^{[1
]}

Foxwell, Brian M. J. ^{[1
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Fac Med, Kennedy Inst Rheumatol Div, London W6 8LH, England

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 370卷 / 04期

基金：

英国医学研究理事会;

关键词：

Bmx; Tec; kinase; TLR; LPS; interieukin-6; VEGF; rheumatoid; synovial fibroblast;

D O I：

10.1016/j.bbrc.2008.03.142

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Discordant cytokine production is characteristic of chronic inflammatory conditions like rheumatoid arthritis (RA), and anti-cytokine therapeutics are becoming routinely used to treat RA in the clinic. Fibroblasts from rheumatoid synovium have been shown to contribute to cytokine production in inflamed joints; likewise these cells also produce cytokines in response to inflammatory mediators signalling through Toll like receptors (TLRs). Tyrosine kinase activity is essential to LPS-induced cytokine production, and we have previously implicated a role for the Tec kinase, Bmx, in inflammatory cytokine production. Here we show that Bmx kinase activity in RASF is increased following LPS stimulation and that Bmx is involved in the regulation of LPS-induced IL-6 and VEGF production via mRNA stabilisation. This is an important insight into the regulation of VEGF, which is involved in a wide range of different pathologies, and may lead to more effective design of novel anti-inflarnmatory/angiogenic therapeutics for conditions such as RA. (c) 2008 Elsevier Inc. All rights reserved.

引用

页码：599 / 602

页数：4

共 20 条

[1] Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis [J].