Tissue inhibitor of metalloproteinases‐2 (TIMP‐2) in rat liver cells is increased by lipopolysaccharide and prostaglandin E2

Abstract
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 E2 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.