title: Oncostatin M pathway plays a major role in the renal acute phase response.
abstract: The acute phase response is traditionally characterized by hepatic synthesis of proteins as an inflammatory response to injury, with interleukin-6 (IL-6) being the key mediator. In contrast, microarray studies in human renal transplant implantation biopsies indicate a strong acute phase response in the deceased donor kidney, associated with a significant upregulation of oncostatin M receptor beta (OSMR). The aim of this study was to determine whether the kidney can generate a strong acute phase response, mediated by the OSM/OSMR gateway. Genes associated with the IL-6 cytokine family and acute phase reactants were analyzed by real-time RT-PCR in four groups of human biopsies spanning a spectrum of renal injury. OSM, OSMR, and fibrinogen beta (FGB) were progressively more highly expressed from prenephrectomy, living donor, deceased donor, to discarded donor kidneys, suggesting correlation with severity of injury and local renal synthesis. Acute phase response gene expression was analyzed in human proximal tubular cells in culture in response to OSM. OSM induced a significant increase in expression of FGB, OSMR, serpin peptidase inhibitor A1, IL-6, and lipopolysaccharide binding protein, and a decrease in IL-6R. These changes were largely attenuated by coincubation with an OSMR blocking antibody, indicating the OSM effect was mediated through OSMR. OSM also resulted in a significantly altered expression of acute phase genes compared with IL-6 or leukemia inhibitory factor, suggesting that OSM is the predominant cytokine mediating the renal tubular acute phase response. In conclusion, the renal parenchyma is capable of generating a strong acute phase response, likely mediated via OSM/OSMR.
authors.affiliation: HMRC 260, Univ. of Alberta, Edmonton, Canada T6G 2S2.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Luyckx
authors.forename: Lucas V
authors.initials: LV
authors.lastname: Cairo
authors.forename: Catharine A
authors.initials: CA
authors.lastname: Compston
authors.forename: Wai Lee
authors.initials: WL
authors.lastname: Phan
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Mueller
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000210:Acute-Phase Reaction / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001706:Biopsy; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D005340:Fibrinogen / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016030:Kidney Transplantation / Q000276:immunology*; D007684:Kidney Tubules / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D019520:Living Donors; D008562:Membrane Glycoproteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D053683:Oncostatin M / Q000235:genetics / Q000378:metabolism*; D053681:Oncostatin M Receptor beta Subunit / Q000235:genetics / Q000378:metabolism*; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D015398:Signal Transduction; D000515:alpha 1-Antitrypsin / Q000378:metabolism; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D005340:Fibrinogen; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D053683:Oncostatin M; D053681:Oncostatin M Receptor beta Subunit; D019947:Receptors, Interleukin-6; D000515:alpha 1-Antitrypsin; D000099231:Lipopolysaccharide-Binding Protein; C508600:IL6 protein, human; C508603:IL6R protein, human; C508348:OSMR protein, human; C043392:SERPINA1 protein, human