title: Regulatory mechanism of transforming growth factor beta receptor type II degradation by interleukin-1 in primary chondrocytes.
abstract: Interleukin-1β (IL-1β), a key-cytokine in osteoarthritis, impairs TGFβ signaling through TβRII down-regulation by increasing its degradation. Here, we investigated the molecular mechanism that controls TßRII fate in IL-1ß treated cells. Chondrocytes were treated with IL-1ß in the presence of different inhibitors. TßRII and Cav-1 expression were assayed by Western blot and RT-PCR. We showed that IL-1ß-induced degradation of TßRII is dependent on proteasome and on its internalization in caveolae. In addition, IL-1ß enhances Cav-1 expression, a major constituent of lipid raft. In conclusion, we enlighten a new mechanism by which IL-1ß antagonizes TGFß pathway and propose a model of TßRII turnover regulation upon IL-1ß treatment.
authors.affiliation: Université de Caen Basse-Normandie, Caen, France. catherie.bauge@unicaen.fr
authors.forename: Catherine
authors.initials: C
authors.lastname: Baugé
authors.forename: Nicolas
authors.initials: N
authors.lastname: Girard
authors.forename: Sylvain
authors.initials: S
authors.lastname: Leclercq
authors.forename: Philippe
authors.initials: P
authors.lastname: Galéra
authors.forename: Karim
authors.initials: K
authors.lastname: Boumédiene
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001692:Biological Transport / Q000187:drug effects; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D021941:Caveolae / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D009761:Nystatin / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects*; D011719:Pyrazines / Q000494:pharmacology; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D001897:Boronic Acids; D051242:Caveolin 1; D053583:Interleukin-1beta; D061988:Proteasome Inhibitors; D011719:Pyrazines; D018125:Receptors, Transforming Growth Factor beta; D009761:Nystatin; D000069286:Bortezomib; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D046988:Proteasome Endopeptidase Complex