Oncostatin M up-regulates the ER chaperone Grp78/BiP in liver cells

Stefan Vollmer (1) , Claude Haan (1) , Iris Behrmann (1)

1 University of Luxembourg [Luxembourg]

OSM, a cytokine of the IL-6 type cytokine family, regulates inflammatory processes (acute phase, tissue remodeling, angiogenesis), cell differentiation and proliferation. Inflammation is discussed to favor carcinogenesis and the inflammatory cytokine OSM was lately described to upregulate HIF-1α, whose upregulation is also observed in many cancers. In this study we demonstrate that OSM, and to a lesser degree by IL-6, induces the expression of Grp78/BiP, an ER chaperone associated with tumor development and poor prognosis in cancer. In contrast, IFN-γ or TNF-α.had no effect on Grp78 expression. The up-regulation seems to be specific to liver cells, as it occurs in hepatocytes and hepatoma cells but not in prostate, melanoma, breast or kidney cells. OSM does not lead to up-regulation of Grp94, enhanced XBP-1 mRNA splicing or phosphorylation of eIF2α, indicating that it is not associated to a general ER stress response. Analysis of the underlying mechanism showed that Grp78 is up-regulated by transcriptional processes which are to the greater part, though not completely, dependent on MEK/Erk activation.

Mots clés: cytokines; Oncostatin M; Grp78/BiP; cytokine signal transduction; Jak/STAT; MAP kinases

Stefan Vollmer, Claude Haan, Iris Behrmann. Oncostatin M up-regulates the ER chaperone Grp78/BiP in liver cells. Biochemical Pharmacology, 2010, 80 (12), pp.2066. ⟨10.1016/j.bcp.2010.07.015⟩. ⟨hal-00637152⟩