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Up-regulation of protease-activated receptor-2 by bFGF in cultured human synovial fibroblasts

Up-regulation of protease-activated receptor-2 by bFGF in cultured human synovial fibroblasts
Up-regulation of protease-activated receptor-2 by bFGF in cultured human synovial fibroblasts
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-1beta 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-NH(2)), but not the inactive reverse peptide (VKGILS-NH(2)), induced transitory cytosolic Ca(2+) 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.
basic fibroblast growth factor, interleukin-1?, synovial fibroblasts, protease-activated receptors, PAR-2 agonist peptide, rheumatoid arthritis, tumor necrosis factor-?
0024-3205
898-904
Abe, Kazuki
c8d13112-dea2-4174-b522-47650ddbbd58
Aslam, Akhmed
c64f28a8-d34d-4253-8351-e9c2f76545e9
Walls, Andrew F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Sato, Toshitsugu
d27ae57a-1c7d-445c-ad60-7f143d643ad0
Inoue, Hideo
8e5f223a-dc1a-453f-bc3c-09d6ec965714
Abe, Kazuki
c8d13112-dea2-4174-b522-47650ddbbd58
Aslam, Akhmed
c64f28a8-d34d-4253-8351-e9c2f76545e9
Walls, Andrew F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Sato, Toshitsugu
d27ae57a-1c7d-445c-ad60-7f143d643ad0
Inoue, Hideo
8e5f223a-dc1a-453f-bc3c-09d6ec965714

Abe, Kazuki, Aslam, Akhmed, Walls, Andrew F., Sato, Toshitsugu and Inoue, Hideo (2006) Up-regulation of protease-activated receptor-2 by bFGF in cultured human synovial fibroblasts. Life Sciences, 79 (9), 898-904. (doi:10.1016/j.lfs.2006.03.034).

Record type: Article

Abstract

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-1beta 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-NH(2)), but not the inactive reverse peptide (VKGILS-NH(2)), induced transitory cytosolic Ca(2+) 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.

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More information

Published date: 24 July 2006
Keywords: basic fibroblast growth factor, interleukin-1?, synovial fibroblasts, protease-activated receptors, PAR-2 agonist peptide, rheumatoid arthritis, tumor necrosis factor-?

Identifiers

Local EPrints ID: 59256
URI: http://eprints.soton.ac.uk/id/eprint/59256
ISSN: 0024-3205
PURE UUID: 6526db94-ba24-4239-baa9-15c09a4afd00

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Date deposited: 02 Sep 2008
Last modified: 13 Mar 2019 20:30

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