Glucocorticoids inhibit oncostatin M-induced phospholipase A(2) gene expression in human hepatoma cells

The secreted phospholipase A(2) (sPLA(2)) is released from hepatoma cells after stimulation with interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta), and is considered to act as acute phase protein, In the present study, the regulation of sPLA(2) secretion by two other members of the IL-6 cytokine family, oncostatin M (OSM) and leukaemia inhibitory factor (LIF), and the corticosteroid dexamethasone were investigated, Only a marginal increase in sPLA(2) activity in cell culture supernatants of HepG2 cells was observed upon stimulation for 24 h with LIF, whereas OSM increased the activity about 10-fold and proved to be even more effective than the combination of IL-6 and TNF-alpha, the best known stimuli so far, sPLA(2) activity was synergistically enhanced by OSM plus TNF-alpha. (15-fold) or IL-1 beta (20-fold), Changes in sPLA(2) activity were reflected at mRNA levels, Cytokine induction of sPLA(2) mRNA was comparable to the induction of haptoglobin mRNA, The effect of dexamethasone on the expression of both genes, in contrast, was different: cytokine-induced haptoglobin mRNA expression was enhanced, whereas sPLA(2) mRNA expression was partially inhibited by dexamethasone resulting in decreased sPLA(2) activity, The strong induction by OSM in HepG2 cells thus confirmed sPLA(2) as acute phase protein, whereas the effect of dexamethasone was comparable to the one observed in other cell types. (C) 1997 Academic Press Limited.