The liver regenerates quickly upon injury and restores its mass to meet the functional requirements of the body.  Although it has been suggested that prostanoids are involved in the process, their role in liver regeneration has not been fully established.  The aim of this study is to determine the role of prostaglandin (PG) I₂ in this phenomenon.
Inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha, are the major priming factors in liver regeneration facilitating the G₁-phase transition of hepatocytes.  TNF-alpha up-regulated the expression level of IL-6 mRNA in cultured wild-type Kupffer cells.  Interestingly, IP agonist significantly increased the TNF-alpha induced up-regulation of IL-6 mRNA, and this accelerative effect of IP agonist disappeared in IP^–/– Kupffer cells.  We next stimulated cultured hepatocytes with TNF-alpha for 72 hours.  After 72 hours, the expression level of IP mRNA increased significantly compared with that in vehicle treatment.  Furthermore, in the TNF-alpha stimulated hepatocytes, IP agonist significantly increased intracellular cAMP production in a concentration-dependent manner.  We next examined whether IP activation can induce phosphorylation of cAMP-regulatory element binding protein (CREB) in the TNF-alpha stimulated hepatocytes using the Western blot assay.  Indeed, IP agonist induced the phosphorylation of CREB, which effect disappeared in vehicle treated WT hepatocytes.  These results suggest that PGI₂ facilitates liver regeneration in cooperation with TNF-alpha.