%0 Journal Article %T Interleukin-27 and IFNγ regulate the expression of CXCL9, CXCL10, and CXCL11 in hepatitis %+ Cytokines : structure, signalisation et prolifération tumorale %+ Laboratoire Interdisciplinaire Carnot de Bourgogne (ICB) %+ Institut de recherche en santé, environnement et travail (Irset) %+ Institut de Génétique et Développement de Rennes (IGDR) %+ Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) %A Basset, Laetitia %A Chevalier, Sylvie %A Danger, Yannic %A Arshad, Muhammad Imran %A Piquet-Pellorce, Claire %A Gascan, Hugues %A Samson, Michel %< avec comité de lecture %@ 0946-2716 %J Journal of Molecular Medicine %I Springer Verlag %V 93 %N 12 %P 1355-1367 %8 2015 %D 2015 %R 10.1007/s00109-015-1319-6 %M 26199110 %K IL-27 %K Liver inflammation %K Hepatic cells %K IFNγ %K CXCR3 ligands %Z Life Sciences [q-bio]Journal articles %X Unlabelled - Interleukin-27 (IL-27) belongs to the IL-6/IL-12 family of cytokines, associated with different inflammatory diseases and orchestrates its biological activity via common heterodimeric receptor composed of WSX-1 (IL-27Rα) and gp130. The present study was aimed to investigate the regulation of CXCL9, CXCL10, and CXCL11 chemokines in hepatic cells (human LX-2 cell line derived from normal human stellate cells (HSC), primary human hepatocytes, HSC, and HepG2 cells) and concanavalin A (ConA)-induced liver inflammation. We demonstrated that IL-27, but not IL-6, induced/up-regulated CXCR3 ligand genes (CXCL9, CXCL10, and CXCL11; out of 26 selected genes) in a STAT1-dependent manner in hepatic cells in vitro both at transcript and protein levels. In ConA-induced T cell-mediated hepatic model, we showed that soluble IL-27/IFNγ was elevated following ConA hepatitis in association with increased CXCL9, CXCL10, and CXCL11 expression in the liver. The exogenous IL-27 administration induced CXCR3 ligands in mouse liver at 4 h with any significant effect on recruitment of CXCR3(+) immune cells in the liver. The neutralization of IL-27 during ConA hepatitis differentially modulated (transcript vs protein expression) CXCR3 ligands and IFNγ during ConA-induced hepatitis with down-regulated expression of CXCL9 and CXCL10 at transcript level. The IFNγ, complementary regulated the expression of CXCR3 ligands as their up-regulation during ConA hepatitis, was abolished in IFNγ KO mice. In summary, IL-27 up-regulated the CXCL9, CXCL10, and CXCL11 chemokine expression in hepatic cells. IL-27 regulated CXCR3 ligand expression in IFNγ-dependent manner during acute hepatitis suggesting a complementary role of IL-27 and IFNγ to moderate liver inflammation via regulation of CXCR3 ligands. Key message - IL-27 up-regulated CXCR3 ligand expression in human hepatic cells in vitro. IL-27 up-regulated CXCR3 ligand expression and secretion in ConA hepatitis in vivo. CXCR3 ligand expression was down-regulated by blocking IL-27 or IFNγ deficiency. IL-27 modulated liver injury by regulation of CXCR3 ligands in IFNγ-dependent manner. %G English %L hal-01214006 %U https://univ-rennes.hal.science/hal-01214006 %~ UNIV-BOURGOGNE %~ UNIV-RENNES1 %~ CNRS %~ UNIV-ANGERS %~ ICB %~ IFR140 %~ IRSET %~ STATS-UR1 %~ IRSET-SMS %~ IRSET-CCII %~ IRSET-TREC %~ IRSET-HIAEC %~ IRSET-SMLF %~ IRSET-ERD %~ IRSET-VCER %~ IRSET-NEED %~ IRSET-TNGC %~ UR1-UFR-SVE %~ UR1-HAL %~ UR1-SDV %~ IRSET-2 %~ TEST-UNIV-RENNES %~ TEST-UR-CSS %~ UNIV-RENNES %~ IRSET-2-EX-HIAEC %~ UR1-BIO-SA