培養ラット血管平滑筋細胞の遊走と増殖におよぼす抗アレルギー薬pemirolastの抑制効果

Abstract

An antiallergic drug, pemirolast potassium (TBX), has been shown to inhibit the release of pro-inflammatory mediators from mast cells and eosinophils through the inhibition of intracellular calcium mobilization and modulation of phosphatidylinositol (PI) turnover.We have studied the effect of TBX on cell proliferation and migration of vascular smooth muscle cells (SMCs) in vitro. SMCs were cultured from rat aorta and were stimulated with fetal calf serum (FCS), platelet-derived growth factor (PDGF), angiotensin II (ATII) or endothelfin I (ET-I).In the cell proliferation assay. DNA synthesis was measured as BrdU incorporation into DNA at 36hr after FCS stimulation. TBX at concentrations from 10-7 to 10-4M inhibited BrdU incorporation into DNA. This finding was consistent with the observation that TBX dose-dependently decreased the number of cells at 24, 36 and 48hr after FCS stimulation. Furthermore, TBX (10-4M) inhibited cell proliferation stimulated with PDGF, ATII or ET-I.On the migration, the effect of TBX at concentrations from 10-7 to 10-4M was examined by Boyden's chamber method. TBX dose-dependently inhibited cell migration as determined by number of cells.Morever, we examined the inhibitory effect of TBX on 1, 4, 5-IP3 formation induced by ATII in SMCs. TBX also suppressed PI turnover.These findings indicated that TBX may intervene initiation and progression of atherosclerosis through the inhibition of proliferation and migration of arterial SMCs. Therefore, TBX may be clinically applicable for the prevention of restenosis after percutaneous transluminal coronary angioplasty.