Oncostatin M synergises with house dust mite proteases to induce the production of PGE(2) from cultured lung epithelial cells

1 The release of PGE(2) and nitric oxide (NO) from the respiratory epitheli um may act to dampen inflammation. In other tissues, oncostatin M (OSM), a potent inducer of epithelial antiproteases, has also been shown to interact with IL-1 beta to stimulate PGE(2) release. However, whether OSM interacts with pro-inflammatory cytokines and proteases in the production of anti-in flammatory eicosanoids and NO from airway epithelium is unknown. 2 The effect of OSM and the related cytokine leukaemia inhibitory factor (L IF) on PGE(2) and NO production by the respiratory epithelial cell line: A5 49 in response to pro-inflammatory cytokines as well as protease-rich house dust mite (HDM) fractions and a protease-deficient rye grass pollen extrac t was examined by immunohistochemistry, cell culture, ELISA and enzyme-immu noassay. 3 Cells treated with a mixture of IL-I beta, IFN gamma and LPS for 48 h pro duced a 9 fold increase in PGE, and a 3 fold increase in NO levels (both P< 0.05). Both OSM and LIF were without effect. However, OSM added together wi th the cytokine mixture synergistically enhanced PGE(2) production (22 fold , P<0.05). OSM also synergistically enhanced PGE(2) production in response to a cysteine protease-enriched, but not serine protease-enriched HDM fract ion (P<0.05). Rye grass extract, neither alone nor in combination with OSM, induced PGE, or NO production, although it did induce the release of GM-CS F. 4 These observations suggest that OSM is an important co-factor in the rele ase of PGE(2) and NO from respiratory epithelial cells and may play a role in defense against exogenous proteases such as those derived from HDM.