Control of LMP7 expression in human endothelial cells by cytokines regulating cellular and humoral immunity

Formation of antigenic peptides by the multicatalytic proteinase complex (MPC, proteasome) is facilitated by incorporation of three subunits (LMP2, LMP7 and LMP10) that are inducible by IFN-γ and TNF-α. These cytokines, or their functional homologues (e.g. TNF-β), are released from many cells including Th₁ lymphocytes. To learn more about the relationship between control of cellular immunity and expression of LMP subunits, we measured LMP7 levels in human umbilical vein endothelial cells of cytokines promoting cellular immunity (IL-12, IFN-γ, TNF-α) or humoral immunity (IL-10, IL-6). Little or no effect was seen when cells were exposed to IL-6, IL-10 or IL-12 alone. IFN-γ upregulated LMP7 levels, as did TNF-α to a lesser extent. IL-10 downregulated IFN-γ-induced increases in LMP7 levels, as did IL-12. The findings indicate that regulation of levels of LMP7 is similar to and may be coupled with that of other molecules required for MHC class I-dependent immunity, and depends primarily on cytokines released by Th₁ helper lymphocytes. (C) 2000 Academic Press.