PMID- 11557268 OWN - NLM STAT- MEDLINE DCOM- 20011101 LR - 20190624 IS - 0014-2999 (Print) IS - 0014-2999 (Linking) VI - 427 IP - 2 DP - 2001 Sep 14 TI - Tranilast inhibits interleukin-1beta-induced monocyte chemoattractant protein-1 expression in rat mesangial cells. PG - 151-8 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-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. FAU - Chikaraishi, A AU - Chikaraishi A AD - Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, 1608582 Tokyo, Japan. FAU - Hirahashi, J AU - Hirahashi J FAU - Takase, O AU - Takase O FAU - Marumo, T AU - Marumo T FAU - Hishikawa, K AU - Hishikawa K FAU - Hayashi, M AU - Hayashi M FAU - Saruta, T AU - Saruta T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-1) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (Recombinant Fusion Proteins) RN - 0 (ortho-Aminobenzoates) RN - EC 1.13.12.- (Luciferases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - HVF50SMY6E (tranilast) SB - IM MH - Animals MH - Cells, Cultured MH - Chemokine CCL2/*genetics MH - Gene Expression Regulation/drug effects MH - Glomerular Mesangium/cytology/*drug effects/metabolism MH - Interleukin-1/*pharmacology MH - Luciferases/genetics/metabolism MH - Mitogen-Activated Protein Kinases/drug effects/metabolism MH - NF-kappa B/genetics/metabolism MH - RNA, Messenger/drug effects/genetics/metabolism MH - Rats MH - Recombinant Fusion Proteins/genetics/metabolism MH - ortho-Aminobenzoates/*pharmacology EDAT- 2001/09/15 10:00 MHDA- 2001/11/03 10:01 CRDT- 2001/09/15 10:00 PHST- 2001/09/15 10:00 [pubmed] PHST- 2001/11/03 10:01 [medline] PHST- 2001/09/15 10:00 [entrez] AID - S0014-2999(01)01215-8 [pii] AID - 10.1016/s0014-2999(01)01215-8 [doi] PST - ppublish SO - Eur J Pharmacol. 2001 Sep 14;427(2):151-8. doi: 10.1016/s0014-2999(01)01215-8.