title: Secretion of oncostatin M by infiltrating neutrophils: regulation of IL-6 and chemokine expression in human mesothelial cells.
abstract: Recently, we identified that regulation of leukocyte recruitment by IL-6 requires shedding of the IL-6R from infiltrating neutrophils. In this study, experiments have examined whether other IL-6-related cytokines possess similar properties. Levels of oncostatin M (OSM) and leukemia inhibitory factor were analyzed in patients with overt bacterial peritonitis during the first 5 days of infection. Although no change in leukemia inhibitory factor was observed throughout the duration of infection, OSM was significantly elevated on day 1 and rapidly returned to baseline by days 2-3. The source of OSM was identified as the infiltrating neutrophils, and OSM levels correlated both with leukocyte numbers and i.p. soluble IL-6R (sIL-6R) levels. FACS analysis revealed that OSM receptor beta expression was restricted to human peritoneal mesothelial cells. Stimulation of human peritoneal mesothelial cells with OSM induced phosphorylation of gp130 and OSM receptor beta, which was accompanied by activation of STAT3 and secretion of CC chemokine ligand 2/monocyte chemoattractant protein-1 and IL-6. Although OSM itself did not modulate CXC chemokine ligand 8/IL-8 release, it effectively suppressed IL-1beta-mediated expression of this neutrophil-activating CXC chemokine. Moreover, OSM synergistically blocked IL-1beta-induced CXC chemokine ligand 8 secretion in combination with the IL-6/sIL-6R complex. Thus suggesting that OSM and sIL-6R release from infiltrating neutrophils may contribute to the temporal switch between neutrophil influx and mononuclear cell recruitment seen during acute inflammation.
authors.affiliation: Cardiff School of Biosciences, Cardiff University, Institute of Nephrology, University of Wales College of Medicine, United Kingdom. Suzanne.Hurst@uwe.ac.uk
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Hurst
authors.forename: Rachel M
authors.initials: RM
authors.lastname: McLoughlin
authors.forename: James
authors.initials: J
authors.lastname: Monslow
authors.forename: Sara
authors.initials: S
authors.lastname: Owens
authors.forename: Llinos
authors.initials: L
authors.lastname: Morgan
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Fuller
authors.forename: Nicholas
authors.initials: N
authors.lastname: Topley
authors.forename: Simon A
authors.initials: SA
authors.lastname: Jones
mesh_terms: D015703:Antigens, CD / Q000502:physiology; D001424:Bacterial Infections / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000096:biosynthesis; D006131:Growth Inhibitors / Q000096:biosynthesis; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000502:physiology; D018375:Neutrophil Activation / Q000276:immunology; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism*; D009852:Omentum / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism* / Q000502:physiology; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects; D010538:Peritonitis / Q000276:immunology; D018121:Receptors, Cytokine / Q000502:physiology; D019947:Receptors, Interleukin-6 / Q000502:physiology; D053677:Receptors, Oncostatin M; D015398:Signal Transduction / Q000276:immunology; D012995:Solubility
chemical_list: D015703:Antigens, CD; D018925:Chemokines; D016207:Cytokines; D006131:Growth Inhibitors; C494199:IL6ST protein, human; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D008562:Membrane Glycoproteins; C508351:OSM protein, human; D010455:Peptides; D018121:Receptors, Cytokine; D019947:Receptors, Interleukin-6; D053677:Receptors, Oncostatin M; D053683:Oncostatin M; D050822:Cytokine Receptor gp130