A histamine gene expression program in human macrophages.
The significance of histamine signaling in septic shock is debated (1-5). The macrophage is one of the critical cell types that provide rapid immune responses to early events in septic shock (6-11). To understand in a systematic and unbiased manner the transcriptional behavior of macrophage in response to the immunologic effector histamine, we used a public dataset (12) to describe the most significant changes in the gene expression program of human primary macrophages from response to histamine exposure. We found that of the genes whose expression was most different between macrophages exposed to histamine and the naïve macrophage there were a selection of the genes whose expression could be assigned to 22 discrete modules, including genes encoding enzymes involved in glycosylation, the mitochondria and metabolism, the quality control and translation of proteins, the ER stress response, the Rab family of molecules, genes that bind or encode molecules involved in genetic and epigenetic modulation of DNA and RNA, CXCL5, and the cyclin dependent kinase CDK14. It appears that macrophages respond to histamine exposure by altering gene expression at a relatively large number of loci but by a relatively small order of magnitude.