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 ce lls after stimulation with interleukin 6 (IL-6), tumour necrosis facto r alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta), and is conside red to act as acute phase protein, In the present study, the regulatio n of sPLA(2) secretion by two other members of the IL-6 cytokine famil y, oncostatin M (OSM) and leukaemia inhibitory factor (LIF), and the c orticosteroid dexamethasone were investigated, Only a marginal increas e 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-f old) or IL-1 beta (20-fold), Changes in sPLA(2) activity were reflecte d 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-induce d haptoglobin mRNA expression was enhanced, whereas sPLA(2) mRNA expre ssion was partially inhibited by dexamethasone resulting in decreased sPLA(2) activity, The strong induction by OSM in HepG2 cells thus conf irmed sPLA(2) as acute phase protein, whereas the effect of dexamethas one was comparable to the one observed in other cell types. (C) 1997 A cademic Press Limited.