Complement factor I is upregulated in rat hepatocytes by interleukin-6 butnot by interferon-gamma, interleukin-1 beta or tumor necrosis factor-alpha

Complement factor I (FI) is a regulatory serine protease of the complement system which cleaves three peptide bonds in the alpha -chain of C3b and two bonds in the alpha -chain of C4b and thus prevents the assembly of the C3 and C5 convertases. We have investigated the proinflammatory cytokines IL-6 , IL-1 beta, TNF-alpha. and IFN-gamma for their potential role in the regul ation of FI expression. Of the investigated cytokines, only IL-6 increased the FI-specific RT-PCR signal in isolated hepatocytes, in the two rat hepat oma-derived cell lines FAO and H4IIE or in HUVECs. Quantitative competitive RT-PCR showed an IL-6 induced upregulation of FI-specific mRNA by about te n-fold. These data are in accord with Northern blot analyses in which the F I-mRNA was upregulated by IL-6 between five- and seven-fold. IL-6, but not IL-1 beta, TNF-alpha or IFN-gamma also increased FI-protein levels in cell culture supernatants by about five-fold as determined by a semiquantitative immunoblot using a novel monoclonal antibody specific for rat FI.