Tranilast inhibits interleukin-1 beta-induced monocyte chemoattractant protein-1 expression in rat mesangial cells

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 dru g, has been demonstrated to have various anti-inflammatory and anti-prolife rative effects, and recently has been reported to prevent restenosis after percutaneous transluminal coronary angioplasty. In this study, we investiga ted whether tranilast inhibits MCP-1 secretion in mesangial cells. Tranilas t inhibited interleukin-1 beta -induced MCP-1 secretion and mRNA expression in a concentration-dependent manner. Luciferase assay showed that tranilas t suppressed interleukin-1 beta -induced nuclear factor-kappaB (NF-kappaB)- dependent transcription. Interleukin-1 beta -induced Jun N-terminal kinase (JNK) activation was also suppressed selectively by tranilast. These result s indicate that tranilast inhibits interleukin-1 beta -induced MCP-1 produc tion, at least in part, by inhibiting NF-kappaB activity and that suppressi on of JNK activation might be involved in the inhibition of MCP-1 productio n. Tranilast may serve as a new therapeutic agent for glomerulonephritis th rough anti-chemokine property. (C) 2001 Elsevier Science B.V. All rights re served.