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

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 infla...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2008-06, Vol.370 (4), p.599-602
Main Authors: Palmer, Christine D., Mutch, Brenda E., Page, Theresa H., Horwood, Nicole J., Foxwell, Brian M.J.
Format: Article
Language:English
Subjects:
Arthritis, Rheumatoid - enzymology
Arthritis, Rheumatoid - immunology
Bmx
Cells, Cultured
Fibroblasts - drug effects
Fibroblasts - enzymology
Fibroblasts - immunology
Humans
Interleukin-6
Interleukin-6 - genetics
Interleukin-6 - metabolism
Kinase
Lipopolysaccharides - immunology
Lipopolysaccharides - pharmacology
LPS
Protein-Tyrosine Kinases - antagonists & inhibitors
Protein-Tyrosine Kinases - genetics
Protein-Tyrosine Kinases - metabolism
Rheumatoid
RNA Stability
Synovial fibroblast
Synovial Membrane - drug effects
Synovial Membrane - enzymology
Synovial Membrane - immunology
Tec
TLR
Vascular Endothelial Growth Factors - genetics
Vascular Endothelial Growth Factors - metabolism
VEGF
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2008.03.142