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

Biochemical and Biophysical Research Communications
Christine D PalmerBrian Michael J Foxwell

Abstract

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-inflammatory/angiogenic therapeutics for conditions such as RA.

References

May 11, 2004·International Archives of Allergy and Immunology·Uwe SchmidtWilfried Ellmeier
Aug 6, 2004·Endocrine Reviews·Napoleone Ferrara
Jun 3, 2005·Nature·Marc Feldmann, Lawrence Steinman
Dec 7, 2007·The Journal of Clinical Investigation·Shahla Abdollahi-RoodsazWim B van den Berg

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Citations

Nov 14, 2012·Nature Reviews. Rheumatology·Nunzio Bottini, Gary S Firestein
Oct 25, 2008·Arthritis Research & Therapy·Stefan K DrexlerBrian M Foxwell
Mar 28, 2012·International Reviews of Immunology·Nicole J HorwoodLynett Danks
Mar 28, 2012·International Reviews of Immunology·Bruno CenniMarie Gottar-Guillier
Oct 24, 2019·Journal of Cellular and Molecular Medicine·Tingting LiuWang Min
Apr 8, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marie Gottar-GuillierBruno Cenni

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