Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 426, Issue 1-2, Pages 113-121Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-2999(01)01209-2
Keywords
lipopolysaccharide; pirfenidone; batimastat; bronchoalveolar lavage; matrix metalloproteinase (MMP); TIMP (tissue inhibitor of matrix metalloproteinase)
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Matrix metalloproteinases (MMPs) are potent to degrade basement membrane collagen associated with acute lung injury in inflammatory processes. We have investigated effects of pirfenidone, antifibrotic agent, and batimastat, inhibitor of MMPs, on gelatinase activities, on release of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), as well as on recruitment of inflammatory cells in bronchoalveolar lavage (BAL) fluid after aerosol administration of lipopolysaccharide (LPS) in mice. Pretreatment with pirfenidone reduced neutrophil recruitment, TNF-alpha and TGF-beta levels, and MMP-9 secretion. In contrast, pretreatment with batimastat (30 or 60 mg/kg, i.p.) only reduced TNF-alpha and TGF-beta levels. Batimastat did not reduce MMP secretion in BAL fluid but inhibited MMP-9 activity. The increase in tissue inhibitor of matrix metalloproteinase (TIMP)-1 induced by LPS was not modified by the two drugs. These findings demonstrate that the two drugs can inhibit the in vivo increase in MMP induced by LPS, batimastat with a direct inhibitor effect on MMP activity and pirfenidone as a consequence of its antiinflammatory effect. (C) 2001 Elsevier Science B.V. All rights reserved.
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