title: Nifedipine, a calcium channel blocker, inhibits inflammatory and fibrogenic gene expressions in advanced glycation end product (AGE)-exposed fibroblasts via mineralocorticoid receptor antagonistic activity.
abstract: Advanced glycation end products (AGE) are involved in tissue damage and remodeling. This study investigated whether AGE could elicit inflammatory and fibrogenic reactions in fibroblast cell line MRC-5 cells via autocrine production of aldosterone and if nifedipine could block the AGE actions through mineralocorticoid receptor (MR) antagonistic activity. AGE significantly up-regulated monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-beta (TGF-beta), type III collagen and receptor for AGE (RAGE) mRNA levels in MRC-5 cells, all of which were completely blocked by nifedipine or an MR antagonist spironolactone. Aldosterone also dose-dependently increased MCP-1, TGF-beta and type III collagen mRNA levels in MRC-5 cells, which were suppressed by nifedipine, but not amlodipine, a control calcium channel blocker. Further, AGE significantly stimulated aldosterone generation in MRC-5 cells, which was partially blocked by nifedipine or spironolactone. In this study, we demonstrated for the first time that AGE could evoke inflammatory and fibrogenic reactions in MRC-5 cells via aldosterone production, which were blocked by the MR antagonistic activity of nifedipine. Our present study provides a unique beneficial aspect of nifedipine on tissue damage and remodeling; it could work as an anti-inflammatory and anti-fibrogenic agent against AGE via MR antagonistic activity.
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsui
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Sho-ichi
authors.initials: S
authors.lastname: Yamagishi
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002460:Cell Line; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D000451:Mineralocorticoid Receptor Antagonists; D009543:Nifedipine / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002121:Calcium Channel Blockers; D017127:Glycation End Products, Advanced; D000451:Mineralocorticoid Receptor Antagonists; D000450:Aldosterone; D009543:Nifedipine