Shan L, Nishimura Y, Kotani Y, Yokoyama M
First Department of Internal Medicine, Kobe University School of Medicine, Japan.
Eur J Pharmacol. 1999 Jun 11;374(1):147-56. doi: 10.1016/s0014-2999(99)00293-9.
Platelet-activating factor (PAF) plays an important role in the pathogenesis of bronchial asthma. To investigate the role of PAF in the maintenance and remodeling of the extracellular matrix, we evaluated the expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 from human bronchial epithelial cells after PAF treatment. Gelatin zymography of human bronchial epithelial cell-conditioned media showed major pro-matrix metalloproteinase-9 and minor pro-matrix metalloproteinase-2 expression and these expressions were totally inhibited by the metalloproteinase inhibitor EDTA. The identification of matrix metalloproteinase-9 was confirmed by Western blot analysis. Northern blotting and zymography demonstrated that PAF induced the mRNA of matrix metalloproteinase-9 from human bronchial epithelial cells and an increase in the gelatinolytic activity of pro-matrix metalloproteinase-9 but not in that of pro-matrix metalloproteinase-2. Lyso-PAF did not induce matrix metalloproteinase-9 mRNA or the gelatinolytic activity of pro-matrix metalloproteinase-9. CV6209, an receptor antagonist of PAF, reduced the increases of pro-matrix metalloproteinase-9 mRNA and gelatinolytic activity induced by PAF. Another receptor antagonist of PAF, hexanolamine PAF, did not inhibit the increases in the synthesis or release of pro-matrix metalloproteinase induced by PAF. Based on these results, we propose that matrix metalloproteinase-9 may be actively involved in the PAF-induced physiopathological remodeling in human bronchial epithelial cells.
