LPS-mediated NFkappaB activation varies between activated human hepatic stellate cells from different donors

The activation of hepatic stellate cells (HSC) is recognized as the key event of hepatic fibrosis [Virchows Arch. 430 (1997) 195; Semin. Liver Dis. 21 (2001) 437; Front. Biosci. 7 (2002) d808]. NFkappaB has been associated with the development of the activated phenotype, the expression of proinflammatory genes, and with promoting survival of activated HSC. High levels of circulating endotoxin are observed in liver fibrosis and several lines of evidence indicate that LPS plays an important role in chronic liver disease. Here, we investigated the LPS-induced NFkappaB activation in activated HSC from different human donors. HSC were isolated from liver specimens obtained during surgical liver resection and were activated by culturing on plastic. LPS-induced NFkappaB activity and IL-8 expression revealed a significant correlation but differed significantly comparing HSC from individual donors. These variations seen in LPS mediated NFkappaB activation and chemokine secretion between HSC from different donors in vitro may contribute to differences seen in vivo between patients in the progression of fibrosis and the degree of inflammation during chronic liver disease.