IFN-gamma increases cathepsin H mRNA levels in mouse macrophages

Expression of major histocompatibility complex (MHC) class II molecules and ability to present antigen to T lymphocytes is acquired upon activation of the macrophage by interferon-gamma (IFN-gamma). Little information is available concerning immune regulation of protease gene expression in mouse macrophages. We have isolated a cDNA clone for Cathepsin H, a lysosomal cysteine proteinase from a cDNA subtraction library of mouse macrophage genes induced by IFN-gamma, and have characterized its expression. The level of Cathepsin H mRNA increased in mouse peritoneal macrophages following addition of IFN-gamma. Cathepsin H mRNA levels began to increase 8 h after the addition of IFN-gamma and was maximal at 24-48 h. This increase was concordant in time with appearance of MHC class II E beta mRNA and Ia invariant chain mRNA. The increase in Cathepsin H mRNA levels by IFN-gamma was dose dependent. Cycloheximide treatment of peritoneal macrophages inhibited the increase in Cathepsin H mRNA levels induced by IFN-gamma, suggesting that the increase in Cathepsin mRNA levels requires de novo protein synthesis. Lipopolysaccharide and cytokines interleukin-2 (IL-2), IL-4, IL-10, and tumor necrosis factor alpha were found to have no effect on Cathepsin H mRNA levels in mouse peritoneal macrophages.