TNF receptor associated factor 5 controls oncostatin M-mediated lung inflammation

Oncostatin M (OSM) is involved in pathogenesis of several human inflammatory diseases including lung inflammation and fibrosis. Although accumulating evidence indicates that OSM mediates lung inflammation, the precise mechanism for OSM on lung inflammation still remains unclear. In this study, we found that OSM receptor was abundantly expressed on endothelial and stromal/fibroblast cells in the lung of mice. In vitro stimulation with OSM upregulated vascular cell adhesion molecule-1 (VCAM-1), which promotes eosinophil infiltration in the lung tissues, on freshly-isolated lung stromal/fibroblast cells from wild-type mice. However, these cells from TNF receptor associated factor 5 (TRAF5)-deficient mice failed to show the increase in VCAM-1 expression after OSM stimulation. Furthermore, Traf5^-/- mice showed markedly attenuated lung inflammation in terms of eosinophil infiltration upon intranasal administration with OSM as compared to wild-type mice. These results indicate that TRAF5 is crucially involved in OSM-mediated lung inflammation probably by inducing lung stromal/fibroblast cell activation.