The regulation of the expression of the interleukin-8 (IL-8) gene in human monocytic cell lines has been investigated. Agents such as interleukin-1 (IL-1) or interferon-γ (IFNγ) did not induce increased IL-8 expression in THP-1 or U937 cells. Bacterial lipopolysaccharide endotoxin (LPS) or phorbol myristate acetate (PMA) alone induced suboptimal expression as assessed by Northern blotting; however, preincubation of cells with PMA followed by endotoxin induced much higher levels of IL-8 mRNA. Incubation of the cells with the calcium ionophore A23187 resulted in consistent increased IL-8 gene expression comparable to that of cells treated with endotoxin alone. In addition to inducing IL-8 mRNA this calcium ionophore also induced IL-8 protein synthesis as assessed by immunofluorescence and secretion as detected by ELISA. These results indicate that increases in intracellular calcium result in IL-8 gene expression and protein secretion.
