TY - JOUR
T1 - Tranilast inhibits interleukin-1β-induced monocyte chemoattractant protein-1 expression in rat mesangial cells
AU - Chikaraishi, Akihiro
AU - Hirahashi, Junichi
AU - Takase, Osamu
AU - Marumo, Takeshi
AU - Hishikawa, Keiichi
AU - Hayashi, Matsuhiko
AU - Saruta, Takao
N1 - Funding Information:
This work was supported in part by a Grant for Scientific Research Expenses for Health and Welfare Programs, with Funds for Comprehensive Research on Chronic Disease (Renal Failure) and New Energy and Industrial Technology Development Organization (NEDO).
Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2001/9/14
Y1 - 2001/9/14
N2 - Monocyte chemoattractant protein-1 (MCP-1), a member of the CC subfamily of chemokines, plays a crucial role in the progression of glomerulonephritis by recruitment of monocytes. Tranilast, a clinically used anti-allergic drug, has been demonstrated to have various anti-inflammatory and anti-proliferative effects, and recently has been reported to prevent restenosis after percutaneous transluminal coronary angioplasty. In this study, we investigated whether tranilast inhibits MCP-1 secretion in mesangial cells. Tranilast inhibited interleukin-1β-induced MCP-1 secretion and mRNA expression in a concentration-dependent manner. Luciferase assay showed that tranilast suppressed interleukin-1β-induced nuclear factor-κB (NF-κB)-dependent transcription. Interleukin-1β-induced Jun N-terminal kinase (JNK) activation was also suppressed selectively by tranilast. These results indicate that tranilast inhibits interleukin-1β-induced MCP-1 production, at least in part, by inhibiting NF-κB activity and that suppression of JNK activation might be involved in the inhibition of MCP-1 production. Tranilast may serve as a new therapeutic agent for glomerulonephritis through anti-chemokine property.
AB - Monocyte chemoattractant protein-1 (MCP-1), a member of the CC subfamily of chemokines, plays a crucial role in the progression of glomerulonephritis by recruitment of monocytes. Tranilast, a clinically used anti-allergic drug, has been demonstrated to have various anti-inflammatory and anti-proliferative effects, and recently has been reported to prevent restenosis after percutaneous transluminal coronary angioplasty. In this study, we investigated whether tranilast inhibits MCP-1 secretion in mesangial cells. Tranilast inhibited interleukin-1β-induced MCP-1 secretion and mRNA expression in a concentration-dependent manner. Luciferase assay showed that tranilast suppressed interleukin-1β-induced nuclear factor-κB (NF-κB)-dependent transcription. Interleukin-1β-induced Jun N-terminal kinase (JNK) activation was also suppressed selectively by tranilast. These results indicate that tranilast inhibits interleukin-1β-induced MCP-1 production, at least in part, by inhibiting NF-κB activity and that suppression of JNK activation might be involved in the inhibition of MCP-1 production. Tranilast may serve as a new therapeutic agent for glomerulonephritis through anti-chemokine property.
KW - MCP-1 (monocyte chemoattractant protein-1)
KW - Mesangial cell
KW - NF-κB (nuclear factor-κB)
KW - Tranilast
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U2 - 10.1016/S0014-2999(01)01215-8
DO - 10.1016/S0014-2999(01)01215-8
M3 - Article
C2 - 11557268
AN - SCOPUS:0035860445
SN - 0014-2999
VL - 427
SP - 151
EP - 158
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2
ER -