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-1beta-induced MCP-1 secretion and mRNA expression in a concentration-dependent
manner. Luciferase assay showed that tranilast suppressed interleukin-1beta-induced
nuclear factor-kappaB (NF-kappaB)-dependent transcription. Interleukin-1beta-induced
Jun N-terminal kinase (JNK) activation was also suppressed selectively by tranilast.
These results indicate that tranilast inhibits interleukin-1beta-induced MCP-1 production,
at least in part, by inhibiting NF-kappaB 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.