Oncostatin M up-regulates the ER chaperone Grp78/BiP in liver cells.
OSM, a cytokine of the IL-6-type cytokine family, regulates inflammatory processes (like the acute phase response), tissue remodeling, angiogenesis, cell differentiation and proliferation. Inflammation is discussed to favor carcinogenesis and the inflammatory cytokine OSM was lately described to up-regulate HIF-1α, whose up-regulation is also observed in many cancers. In this study we demonstrate that OSM, and to a lesser degree 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.
Vollmer
Stefan
S
Life Sciences Research Unit-Signal Transduction Laboratory, University of Luxembourg, 162A, av. de la Faïencerie, 1511 Luxembourg, Luxembourg.
Haan
Claude
C
Behrmann
Iris
I
D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology / Q000502:physiology; D053612:Janus Kinases / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology; D053683:Oncostatin M / Q000494:pharmacology / Q000502:physiology*; D009928:Organ Specificity; D050796:STAT3 Transcription Factor / Q000502:physiology; D014158:Transcription, Genetic; D015854:Up-Regulation
D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D015850:Interleukin-6; D008565:Membrane Proteins; D050796:STAT3 Transcription Factor; C018551:glucose-regulated proteins; D053683:Oncostatin M; D053612:Janus Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3