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.