Glucocorticoids inhibit oncostatin M-induced phospholipase A2 gene expression in human hepatoma cells.
The secreted phospholipase A2 (sPLA2) 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 sPLA2 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 sPLA2 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. sPLA2 activity was synergistically enhanced by OSM plus TNF-alpha (15-fold) or IL-1 beta (20-fold). Changes in sPLA2 activity were reflected at mRNA levels. Cytokine induction of sPLA2 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 sPLA2 mRNA expression was partially inhibited by dexamethasone resulting in decreased sPLA2 activity. The strong induction by OSM in HepG2 cells thus confirmed sPLA2 as acute phase protein, whereas the effect of dexamethasone was comparable to the one observed in other cell types.
Haselmann
J
J
Department of Medicine IV, University of Erlangen-Nürnberg, Germany.
Goppelt-Struebe
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006242:Haptoglobins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D008113:Liver Neoplasms / Q000378:metabolism*; D008222:Lymphokines / Q000494:pharmacology; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D010741:Phospholipases A / Q000235:genetics*; D054467:Phospholipases A2; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000970:Antineoplastic Agents; D005938:Glucocorticoids; D006131:Growth Inhibitors; D006242:Haptoglobins; D007375:Interleukin-1; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; C508351:OSM protein, human; D010455:Peptides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D053683:Oncostatin M; D003907:Dexamethasone; D010741:Phospholipases A; D054467:Phospholipases A2