期刊
LIFE SCIENCES
卷 79, 期 9, 页码 898-904出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2006.03.034
关键词
basic fibroblast growth factor; interleukin-1 beta; synovial fibroblasts; protease-activated receptors; PAR-2 agonist peptide; rheumatoid arthritis; tumor necrosis factor-alpha
资金
- MRC [G0500729] Funding Source: UKRI
- Medical Research Council [G0500729] Funding Source: Medline
- Medical Research Council [G0500729] Funding Source: researchfish
Protease-activated receptors (PARs) have been implicated in the development of acute and chronic inflammatory responses. We have examined the expression of mRNA for PARs and their regulation by growth factors and cytokines in synovial fibroblasts derived from patients with rheumatoid arthritis (RA). Messenger RNA for PAR-1, -2 and -3 was detected in these cells, but not that for PAR-4. Expression of mRNA for PAR-2 was up-regulated by bFGF in a concentration-dependent manner, whereas expression of mRNA for PAR-1 and PAR-3 was not affected. Levels of mRNA encoding PAR-1, PAR-2 and PAR-3 did not increase in response to IL-1 beta and TNF-alpha. Expression of mRNA for PAR-2 was maximal 12 h after addition of bFGF, and maximal levels of immunoreactive PAR-2 were reached after 24 h. Furthermore, PAR-2 agonist peptide (SLIGKV-NH2), but not the inactive reverse peptide (VKGILS-NH2), induced transitory cytosolic Ca2+ mobilization in cells, and its response was increased by pretreatment with bFGF. An important role could be played by bFGF in the regulation of functional PAR-2 expression in cultured RA synovial fibroblasts. (c) 2006 Elsevier Inc. All rights reserved.
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