title: Oncostatin M induces IL-33 expression in liver endothelial cells in mice and expands ST2+CD4+ lymphocytes.
abstract: Interleukin (IL)-33 is crucially involved in liver pathology and drives hepatoprotective functions. However, the regulation of IL-33 by cytokines of the IL-6 family, including oncostatin M (OSM) and IL-6, is not well studied. The aim of the present study was to determine whether OSM mediates regulation of IL-33 expression in liver cells. Intramuscular administration in mice of an adenovirus encoding OSM (AdOSM) leads to increase in expression of OSM in muscles, liver, and serum of AdOSM-infected mice compared with control mice. The increase of circulating OSM markedly regulated mRNA of genes associated with blood vessel biology, chemotaxis, cellular death, induction of cell adhesion molecules, and the alarmin cytokine IL-33 in liver. Steady-state IL-33 mRNA was upregulated by OSM at an early phase (8 h) following AdOSM infection. At the protein level, the expression of IL-33 was significantly induced in liver endothelial cells [liver sinusoidal endothelial cells (LSEC) and vascular endothelial cells] with a peak at 8 days post-AdOSM infection in mice. In addition, we found OSM-stimulated human microvascular endothelial HMEC-1 cells and human LSEC/TRP3 cells showed a significant increase in expression of IL-33 mRNA in a dose-dependent manner in cell culture. The OSM-mediated overexpression of IL-33 was associated with the activation/enrichment of CD4(+)ST2(+) cells in liver of AdOSM-infected mice compared with adenovirus encoding green fluorescent protein-treated control mice. In summary, these data suggest that the cytokine OSM regulates the IL-33 expression in liver endothelial cells in vivo and in HMEC-1/TRP3 cells in vitro and may specifically expand the target CD4(+)ST2(+) cells in liver.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1085, Institut de Recherche Santé Environnement et Travail, Rennes, France; Université de Rennes 1, Rennes, France; Structure Fédérative BioSit UMS 3480 Centre National de la Recherche Scientifique-US18 Institut National de la Santé et de la Recherche Médicale, Rennes, France;
authors.forename: Muhammad Imran
authors.initials: MI
authors.lastname: Arshad
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR 957, Equipe Labellisée LIGUE 2012, Nantes, France;
authors.forename: Pierre
authors.initials: P
authors.lastname: Guihard
authors.affiliation: Structure Fédérative BioSit UMS 3480 Centre National de la Recherche Scientifique-US18 Institut National de la Santé et de la Recherche Médicale, Rennes, France; EFS, Rennes, France.
authors.forename: Yannic
authors.initials: Y
authors.lastname: Danger
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1085, Institut de Recherche Santé Environnement et Travail, Rennes, France; Université de Rennes 1, Rennes, France; Structure Fédérative BioSit UMS 3480 Centre National de la Recherche Scientifique-US18 Institut National de la Santé et de la Recherche Médicale, Rennes, France;
authors.forename: Gregory
authors.initials: G
authors.lastname: Noel
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1085, Institut de Recherche Santé Environnement et Travail, Rennes, France; Université de Rennes 1, Rennes, France; Structure Fédérative BioSit UMS 3480 Centre National de la Recherche Scientifique-US18 Institut National de la Santé et de la Recherche Médicale, Rennes, France;
authors.forename: Jacques
authors.initials: J
authors.lastname: Le Seyec
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR 957, Equipe Labellisée LIGUE 2012, Nantes, France;
authors.forename: Marie-Astrid
authors.initials: MA
authors.lastname: Boutet
authors.affiliation: McMaster Immunology Research Center, McMaster University, Hamilton, Ontario, Canada;
authors.forename: Carl D
authors.initials: CD
authors.lastname: Richards
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1085, Institut de Recherche Santé Environnement et Travail, Rennes, France; Université de Rennes 1, Rennes, France; Structure Fédérative BioSit UMS 3480 Centre National de la Recherche Scientifique-US18 Institut National de la Santé et de la Recherche Médicale, Rennes, France;
authors.forename: Annie
authors.initials: A
authors.lastname: L'Helgoualc'h
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1085, Institut de Recherche Santé Environnement et Travail, Rennes, France; Université de Rennes 1, Rennes, France; Structure Fédérative BioSit UMS 3480 Centre National de la Recherche Scientifique-US18 Institut National de la Santé et de la Recherche Médicale, Rennes, France;
authors.forename: Valentine
authors.initials: V
authors.lastname: Genet
authors.affiliation: Université de Rennes 1, Rennes, France; Service de Biochimie Centre Hospitalier Universitaire Rennes, Université de Rennes 1, Rennes, France;
authors.forename: Catherine
authors.initials: C
authors.lastname: Lucas-Clerc
authors.affiliation: Centre National de la Recherche Scientifique, UMR 6290, Institute of Genetics and Development of Rennes, Rennes, France; and.
authors.forename: Hugues
authors.initials: H
authors.lastname: Gascan
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR 957, Equipe Labellisée LIGUE 2012, Nantes, France;
authors.forename: Frédéric
authors.initials: F
authors.lastname: Blanchard
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1085, Institut de Recherche Santé Environnement et Travail, Rennes, France; Université de Rennes 1, Rennes, France; Structure Fédérative BioSit UMS 3480 Centre National de la Recherche Scientifique-US18 Institut National de la Santé et de la Recherche Médicale, Rennes, France;
authors.forename: Claire
authors.initials: C
authors.lastname: Piquet-Pellorce
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1085, Institut de Recherche Santé Environnement et Travail, Rennes, France; Université de Rennes 1, Rennes, France; Structure Fédérative BioSit UMS 3480 Centre National de la Recherche Scientifique-US18 Institut National de la Santé et de la Recherche Médicale, Rennes, France; michel.samson@univ-rennes1.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Samson
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D018929:Cell Culture Techniques; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006131:Growth Inhibitors / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D000067596:Interleukin-33 / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053683:Oncostatin M / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D006131:Growth Inhibitors; D000067596:Interleukin-33; C508351:OSM protein, human; D012333:RNA, Messenger; D053683:Oncostatin M
keywords: ST2; adenovirus; interleukin-33