Endotoxin induces the expression of prostaglandin H synthase-2 and eicosanoid formation in cells of the human monocytic cell line Mono Mac 6

In controlling inflammation, monocytes and macrophages not only secrete various cytokines but also eicosanoids. Since the human monocytic cell line, Mono Mac 6, represents cells at the stage of mature blood monocytes, cells of this line were investigated to find out whether they also resemble mature monocytes with respect to inflammation. In response to lipopolysaccharide (LPS), Mono Mac 6 cells secreted large amounts of eicosanoids, 6-keto-prostaglandin F_1α (6k-PGF_1α), thromboxane B₂ (TXB₂) and prostaglandin E₂ (PGE₂). The considerable increase in eicosanoid secretion is attributed to the expression of the inducible isoform of the prostaglandin H synthase (PGHS-2) since the PGHS-2-specific steady-state mRNA level, PGHS-2 protein, and the enzyme activity of PGHS were strikingly increased in the absence of detectable PGHS-1 protein. PGHS-2 expression was inhibited by either dexamethasone or cycloheximide. The non-steroidal anti-inflammatory drug (NSAID) diclofenac inhibited the increased PGHS activity. The expression of the PGHS-2 gene was accompanied by the formation of TNFα, IL-6 and IL-8, but not by IL-1β.