Expression of the human complement C8 subunits is independently regulated by interleukin 1β, interleukin 6, and interferon γ

Abstract

The eighth component of human complement (C8) is composed of two subunits which are products from three separate genes. The α-γ- and the β-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-1β,IL-6 and IFN-γ. The effect of the different cytokines on the expression of these subunits was examined using biosynthetical labelling and immunoprecipitation methods. C8α-γ is expressed first and secreted independently from C8β. After 5 h labelling, the expression is strongly reduced, and the majority of C8α-γ is found in the supernatant. C8β expression exhibits a different pattern with a much slower rate of biosynthesis and secretion. Evidence was obtained for an independent secretion of the C8β chain. C8 α-γ expression is strongly enhanced after stimulation with the cytokines IL-6, IFN-γ and IL-1β. In contrast, only IFN-γ but not IL-6 and IL-1β had an increasing effect on the expression of C8β. Thus the total amount of assembled functionally active C8 appears to be limited by the rate of C8β expression.