Expression of the human complement C8 subunits is independently regulated by interleukin 1 beta, interleukin 6, and...

The eighth component of human complement (C8) is composed of two subunits which are products from three separate genes. The alpha-gamma- and the beta-subunit of C8 are expressed independently, and are part of the membrane attack complex. C8 is primarily synthesized in the liver. It has been shown in previous studies that the human hepatoma cell line HepG2 constitutively expresses C8, and thus is a suitable model system for studying C8 biosynthesis in vitro. Expression is modulated by the cytokines IL-1 beta, IL-6 and IFN-gamma. The effect of the different cytokines on the expression of these subunits was examined using biosynthetical labelling and immunoprecipitation methods. C8 alpha-gamma is expressed first and secreted independently from C8 beta. After 5 h labelling, the expression is strongly reduced, and the majority of C8 alpha-gamma is found in the supernatant. C8 beta expression exhibits a different pattern with a much slower rate of biosynthesis and secretion. Evidence was obtained for an independent secretion of the C8 beta chain. C8 alpha-gamma expression is strongly enhanced after stimulation with the cytokines IL-6, IFN-gamma and IL-1 beta. In contrast, only IFN-gamma but not IL-6 and IL-1 beta had an increasing effect on the expression of C8 beta. Thus the total amount of assembled functionally active C8 appears to be limited by the rate of C8 beta expression.