Expression analysis of the human caspase-1 subfamily reveals specific regulation of the CASP5 gene by lipopolysaccharide and interferon-gamma

Based on high sequence homology, there are six members in the caspase-1 sub family: caspases 1, 4, 5, and 13 in humans and caspases 1, 11, and 12 in mi ce. Only caspase-1 is known to activate interleukin-1 beta and interleukin- 18, and caspase-11 activates pro-caspase-1 in vivo. Almost nothing is known about caspases 4, 5, and 13. Here we report a sensitive and specific polym erase chain reaction system to analyze closely related genes. We employed t his system to analyze the gene expression and regulation of human caspases 1, 4, 5, and 13, demonstrating that they have different expression patterns in normal tissues and cell lines, Interferon-gamma strongly induced CASP1 and CASP5 but not CASP4 or CASP13 gene expression in HT-29 colon carcinoma cells. In contrast to the mRNA, interferon-gamma up-regulated caspase-1 but not caspase-5 protein. In the monocytic cell line THP-1, CASP1 mRNA and ca spase-1 protein are expressed constitutively, and their levels were not inc reased by lipopolysaccharide, whereas both GASPS mRNA and caspase-5 protein were induced by lipopolysaccharide. Caspase-1 subfamily members displayed different in vitro activities toward pro-caspases 1 and 3 and pro-interleuk in-1 beta. Our results demonstrate that caspase-1 and caspase-5 levels are modulated by interferon-gamma and lipopolysaccharide, respectively, and sug gest that caspase-1 subfamily members are differentially regulated and may have distinct functions.