IFN-GAMMA INCREASES CATHEPSIN-H MESSENGER-RNA LEVELS IN MOUSE MACROPHAGES

Expression of major histocompatibility complex (MHC) class II molecule s and ability to present antigen to T lymphocytes is acquired upon act ivation of the macrophage by interferon-gamma (IFN-gamma). Little info rmation is available concerning immune regulation of protease gene exp ression in mouse macrophages. We have isolated a cDNA clone for cathep sin H, a lysosomal cysteine proteinase from a cDNA subtraction library of mouse macrophage genes induced by IFN-gamma, and have characterize d its expression. The level of cathepsin H mRNA increased in mouse per itoneal macrophages following addition of IFN-gamma, Cathepsin H mRNA levels began to increase 8 h after the addition of IFN-gamma and was m aximal at 24-48 h, This increase was concordant in time with appearanc e of MHC class II E beta mRNA and Ia invariant chain mRNA, The increas e in cathepsin H mRNA levels by IFN-gamma was dose dependent. Cyclohex imide treatment of peritoneal macrophages inhibited the increase in ca thepsin H mRNA levels induced by IFN-gamma, suggesting that the increa se in cathepsin mRNA levels requires de novo protein synthesis. Lipopo lysaccharide and cytokines interleukin-2 (IL-2), IL-4, IL-10, and tumo r necrosis factor alpha were found to have no effect on cathepsin H mR NA levels in mouse peritoneal macrophages.