Tranilast inhibits interleukin-1beta-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 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.
Chikaraishi
A
A
Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, 1608582 Tokyo, Japan.
Hirahashi
J
J
Takase
O
O
Marumo
T
T
Hishikawa
K
K
Hayashi
M
M
Saruta
T
T
D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D018932:Chemokine CCL2; D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D062367:ortho-Aminobenzoates; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases; C012293:tranilast