Human intrahepatic biliary epithelial cell as a possible modulator of hepatic regeneration: Potential role of biliary epithelial cell for hepatic remodeling in vivo

Abstract

During liver regeneration, the process of hepatic wound healing, a complex cascade of inflammatory signals, recruit inflammatory cells, stimulate hepatobiliary cell proliferation, direct cell migration and induce vascularization to restore tissue integrity, irrespective of its etiology. This might also be the case in cholangiopathies, in which the initial target is the branch of the intrahepatic biliary tree; that is, primary biliary cirrhosis. Previous studies about biliary wound healing focused mainly on the inducers of compensatory biliary proliferation following bile duct insult. Nevertheless, the microenvironment around biliary wound healing responses, which in turn might affect hepatic remodeling, possibly by biliary epithelial cells themselves via paracrine manner, is still less known. In this study, we defined the humoral factors that are released from human intrahepatic biliary epithelial cell lines (HIBEC) with human cytokine array, and reviewed their relevance according to the previous published work. Conditioned medium of HIBEC were revealed to be rich in multiple cytokines and chemokines, including ELR(+)CXC chemokines, such as interleukin-8/CXCL8, growth-related oncoprotein (GRO), epithelial neutrophil chemoattractant (ENA-78), known chemoattractants with a wide range of non-leukocytic activities. Subsequent enzyme-linked immunosorbent assay analyses confirmed that the secretion was commonly observed in various culture conditions and in both an apical and basolateral direction. Considering that some of these factors had been already reported to have direct autocrine mitogenic influence on HIBEC, these findings could further strengthen an active role of HIBEC as a modulator of hepatic regeneration, through its biological reactivity on inflamed milieu.