Enhancement of anti-inflammatory tendency by SB203580, p38alpha specific inhibitor, in human fibroblast-like synoviocyte cell line, MH7A

Seon Kyu Han; Su Jin Jeon; Keiji Miyazawa; Seh Yoon Yi; Young Sook Yoo

doi:10.1007/s00296-006-0109-4

Enhancement of anti-inflammatory tendency by SB203580, p38alpha specific inhibitor, in human fibroblast-like synoviocyte cell line, MH7A

Rheumatol Int. 2006 Sep;26(11):972-8. doi: 10.1007/s00296-006-0109-4. Epub 2006 Mar 11.

Authors

Seon Kyu Han¹, Su Jin Jeon, Keiji Miyazawa, Seh Yoon Yi, Young Sook Yoo

Affiliation

¹ Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, PO Box 131, 130-650, Cheongryang, Seoul, Korea.

PMID: 16532349
DOI: 10.1007/s00296-006-0109-4

Abstract

Interleukin-1 beta (IL-1beta) is an abundant cytokine, which, together with TNF-alpha, mediates inflammatory events in rheumatoid arthritis (RA). IL-1beta is known to induce the induction of inflammatory cytokines and metalloproteinases (MMPs) in rheumatoid synovial cells. Here, we assessed these inflammatory events by measuring IL-1beta levels in the human synovial cell line, MH7A. We observed that the activation of p38 MAP kinase by IL-1beta was involved in the induction of inflammatory cytokines, as well as several genes, including MMP-1 and MMP-3. SB203580, a specific p38 MAP kinase inhibitor, inhibited the production of IL-1beta-induced cytokines and MMPs, while the levels of the tissue inhibitor of metalloproteinase (TIMPs) were unchanged by treatment with SB203580. Moreover, the induction of suppressor of cytokine signaling 3 (SOCS3) and interferon regulatory factor 1 (IRF-1) were both found to be induced by the inhibition of p38 MAP kinase. Therefore, we suggested that the inhibition of p38 MAP kinase might enhance anti-inflammatory tendencies in the MH7A cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Arthritis, Rheumatoid / metabolism
Cell Line
Down-Regulation
Enzyme Inhibitors / pharmacology*
Fibroblasts / enzymology*
Fibroblasts / metabolism
Humans
Imidazoles / pharmacology*
Interleukin-1beta / metabolism
Interleukin-6 / biosynthesis
Interleukin-6 / genetics
Matrix Metalloproteinase 3 / genetics
Matrix Metalloproteinase 3 / metabolism
Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors*
Phosphorylation
Promoter Regions, Genetic
Pyridines / pharmacology*
RNA, Messenger / metabolism
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins / genetics
Suppressor of Cytokine Signaling Proteins / metabolism
Synovial Membrane / enzymology*

Substances

Anti-Inflammatory Agents, Non-Steroidal
Enzyme Inhibitors
Imidazoles
Interleukin-1beta
Interleukin-6
Pyridines
RNA, Messenger
SOCS3 protein, human
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins
Mitogen-Activated Protein Kinase 14
Matrix Metalloproteinase 3
SB 203580