Oncostatin M synergises with house dust mite proteases to induce the production of PGE₂ from cultured lung epithelial cells

The release of PGE₂ and nitric oxide (NO) from the respiratory epithelium 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-1β to stimulate PGE₂ release. However, whether OSM interacts with pro-inflammatory cytokines and proteases in the production of anti-inflammatory eicosanoids and NO from airway epithelium is unknown.

The effect of OSM and the related cytokine leukaemia inhibitory factor (LIF) on PGE₂ and NO production by the respiratory epithelial cell line, A549 in response to pro-inflammatory cytokines as well as protease-rich house dust mite (HDM) fractions and a protease-deficient rye grass pollen extract was examined by immunohistochemistry, cell culture, ELISA and enzyme-immunoassay.

Cells treated with a mixture of IL-1β, IFNγ and LPS for 48 h produced a 9 fold increase in PGE₂ and a 3 fold increase in NO levels (both P<0.05). Both OSM and LIF were without effect. However, OSM added together with the cytokine mixture synergistically enhanced PGE₂ production (22 fold, P<0.05). OSM also synergistically enhanced PGE₂ production in response to a cysteine protease-enriched, but not serine protease-enriched HDM fraction (P<0.05). Rye grass extract, neither alone nor in combination with OSM, induced PGE₂ or NO production, although it did induce the release of GM-CSF.

These observations suggest that OSM is an important co-factor in the release of PGE₂ and NO from respiratory epithelial cells and may play a role in defense against exogenous proteases such as those derived from HDM.