Oncostatin M synergises with house dust mite proteases to induce the production of PGE(2) from cultured lung epithelial cells.
The release of PGE(2) 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-1beta to stimulate PGE(2) 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 PGE(2) 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-1beta, IFNgamma and LPS for 48 h produced a 9 fold increase in PGE(2) 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 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 fraction (P<0.05). Rye grass extract, neither alone nor in combination with OSM, induced PGE(2) 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 PGE(2) and NO from respiratory epithelial cells and may play a role in defense against exogenous proteases such as those derived from HDM.
Knight
D A
DA
Asthma & Allergy Research Institute, University of Western Australia, Nedlands, Western Australia. dknight@cyllene.uwa.edu.au
Asokananthan
N
N
Watkins
D N
DN
Misso
N L
NL
Thompson
P J
PJ
Stewart
G A
GA
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D004357:Drug Synergism; D010450:Endopeptidases / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008129:Lolium / Q000737:chemistry; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008925:Mites / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D011058:Pollen / Q000737:chemistry; D018121:Receptors, Cytokine / Q000032:analysis; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M
D016207:Cytokines; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines; C508351:OSM protein, human; D010455:Peptides; D010936:Plant Extracts; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D053683:Oncostatin M; D009569:Nitric Oxide; D010450:Endopeptidases; D015232:Dinoprostone