Differential regulation of anti-inflammatory proteins in human rheumatoid synoviocyte MH7A cell by celecoxib and ibuprofen.
Non-steroidal anti-inflammatory drugs are known to be the most widely used drugs to exert their anti-inflammatory activities. It was examined protein expression profiles of human rheumatoid fibroblast-like synoviocyte MH7A cells treated with celecoxib, a selective cyclooxygenase-2 inhibitor, or ibuprofen, a non-selective cyclooxygenase inhibitor, using two-dimensional gel electrophoresis for comparison the mechanism of the drugs. Altered expression pattern in response to celecoxib is significantly different from that of ibuprofen treated cells. When MH7A cells were treated with celecoxib, 28 proteins were affected at their expression levels. Among them, heat shock proteins (Hsp60 and 70), glucose regulated proteins (Hsp75 and 78) were observed to be up-regulated by 1 to 30 microM concentrations of celecoxib but those proteins were not affected in ibuprofen treated cells. On the other hand, the expression of 19 proteins was changed by ibuprofen and the expression of apolipoprotein E, RNA binding motif 4, CTP-phosphocholine cytidylyltransferase, and phospholipase A2 inhibitory protein was only altered by ibuprofen. The expressions of 15 proteins were affected by both celecoxib and ibuprofen. Our results showed that celecoxib and ibuprofen, though they are known to act as cyclooxygenase inhibitors, could exert a different mode of acting mechanisms in anti-inflammatory processes. The chemical proteomic approach will be useful for figuring out the mode of actions of drugs.
Heum Park
Jong
J
Korea Research Institute of Bioscience and Biotechnology, Taejeon, Republic of Korea.
Cho Han
Dong
D
Kim
Jina
J
Hyung Hong
Su
S
Lee
Su-Kyung
SK
Seog Yoon
Kab
K
Min Kim
Jung
J
Son
Kwang-Hee
KH
Miyazawa
Keiji
K
Kwon
Byoung-Mog
BM
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D000068579:Celecoxib; D002460:Cell Line; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D013058:Mass Spectrometry; D014176:Protein Biosynthesis / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D007052:Ibuprofen