Reduction of matrix metalloproteinase-9 activity by the selective phosphodiesterase 4 inhibitor, RP 73-401 in sensitized mice

Matrix metalloproteinases are particularly potent in degrading basement mem brane collagen and other extracellular matrix components. We have investiga ted the effects of a selective phosphodiesterase 4 inhibitor, RP 73-401 [N- (3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-methoxybenzamide], on gelatinas e (matrix metalloproteinase-2 and matrix metalloproteinase-9) activity in o valbumin-sensitized and -challenged mice. Twenty-four hours after the last challenge, matrix metalloproteinase activity was evaluated in the bronchoal veolar lavage fluids by a zymography technique, and a significant increase in matrix metalloproteinase-9, but not matrix metalloproteinase-2, activity was noted. When administered orally (0.3-3 mg/kg) 1 h before each ovalbumi n challenge, the selective phosphodiesterase 4 inhibitor, RP 73-401, signif icantly reduced this increased matrix metalloproteinase-9 activity in bronc hoalveolar lavage fluids. Our data suggest that RP 73-401 may modulate tiss ue remodelling associated with lung inflammatory processes including asthma . (C) 2000 Elsevier Science B.V. All rights reserved.