TISSUE INHIBITOR OF METALLOPROTEINASES-2 (TIMP-2) IN RAT-LIVER CELLS IS INCREASED BY LIPOPOLYSACCHARIDE AND PROSTAGLANDIN E(2)

To explore the functional role of TIMP-2 in liver, we determined TIMP-2 mRNA levels in primary rat hepatocytes and in total rat liver, Rat hepatocytes constitutively express TIMP-2 mRNA at a low level, Incubation with dexamethasone, prostaglandin E(2) and a combination of inflammatory cytokines leads to an up-regulation of TIMP-2 mRNA. In rats in vivo we found a dramatic increase of TIMP-2 expression after intraperitoneal injection of lipopolysaccharide. Compared to our previous findings on TIMP-1 we conclude that TIMP-2 mRNA expression is regulated in a distinct and partially opposite manner. Over-production of TIMP-2 could inhibit the activity of metalloproteinases and thus lead to matrix accumulation, Dysregulation of TIMP-2 synthesis might be involved in the development of liver fibrosis.