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

Darryl A. Knight, Nithiananthan Asokananthan, D. Neil Watkins, Neil L.A. Misso, Philip J. Thompson, Geoffrey A. Stewart

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15 Citations (Scopus)

Abstract

1. 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. 2. 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. 3. 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. 4. 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.

Original languageEnglish
Pages (from-to)465-472
Number of pages8
JournalBritish Journal of Pharmacology
Volume131
Issue number3
DOIs
Publication statusPublished - 1 Jan 2000
Externally publishedYes

Keywords

  • Cytokine
  • Dust mites
  • Epithelium
  • Inflammation
  • Oncostatin M

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