Rat gastric gelatinase induction during endotoxemia.

ABSTRACT

Despite continued investigation, the pathogenesis of tissue injury secondary to sepsis remains elusive. Further evaluation of the mechanisms by which endotoxemia and sepsis induce tissue injury is necessary to formulate rational and effective treatment strategies. The purpose of these studies was to evaluate the role of the matrix metalloproteinases MMP-2 and MMP-9 in gastric injury during lipopolysaccharide induced endotoxemia. Lipopolysaccharide increased gastric gelatinase activity as determined by in situ and gelatin zymography. Specifically, lipopolysaccharide induced MMP-2, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) transcription, with subsequent increases in MMP-2 and TIMP-1 protein expression. Furthermore, selective metalloproteinase inhibition ameliorated gastric injury in this model. These data suggest that lipopolysaccharide-induced gastric injury is mediated, at least in part, by increased MMP-2 production.