P009 The innate cytokines IL-1α and TNF-α induce the expression of Oncostatin M and its type II receptor in human colonic subepithelial myofibroblasts
E. Filidou1, G. Kokkotis2, G. Tarapatzi1, M. Boulkou3, K. Arvanitidis1, I. Drygiannakis3, V. Valatas3, I. Koutroubakis3, S. Vradelis4, G. Kolios1, G. Bamias2
1Laboratory of Pharmacology, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece, 2GI Unit, 3rd Academic Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece, 3Laboratory of Gastroenterology, Department of Medicine, University of Crete, Heraklion, Greece, 4University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece
Background
Oncostatin M (OSM), a cytokine of the IL-6 family, has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Specifically, OSM and its receptor, OSMR, are elevated in inflamed colonic regions of IBD patients; in addition, high OSM expression at baseline has been associated with failure to respond to anti-TNF. OSMR expression localised in stromal cells of the intestinal lamina propria. Our aim was to investigate the expression of OSM and its receptors subunits, OSMR, LIFR and gp-130 in primary subepithelial myofibroblasts (SEMFs) and test whether this expression is regulated by the innate cytokines, IL-1α and TNF-α.
Methods
Primary SEMFs were isolated from endoscopically-obtained colonic biopsies from healthy controls, set to culture and stimulated with 5ng/ml IL-1α and/or 50ng/ml TNF-α for 6 h. Total RNA was extracted and the mRNA transcripts for OSM, OSMR, LIFR and gp-130 were measured by reverse transcription-quantitative (RT-q) PCR.
Results
Unstimulated SEMFs had a basal expression of both OSM and its receptors subunits. IL-1α or TNF-α stimulations did not alter LIFR expression, but they induced a statistically significant upregulation of OSM, OSMR and gp-130. Specifically, the expression of OSM in SEMFs was significantly upregulated after stimulation with IL-1α alone or in combination with TNF-α (IL-1α: 11.48-fold increase, 8.29–26.05; IL-1α+TNF-α: 13.42-fold, 11.32–17.16;
Conclusion
Our results show that OSM and OSMR are expressed on primary human SEMFs and that they are upregulated under stimulation with innate pro-inflammatory cytokines. These data further support a potential role of this system of inflammatory mediators in the pathogenesis of intestinal inflammation.