Regulatory mechanism of transforming growth factor beta receptor type II degradation by interleukin-1 in primary chondrocytes

AbstractInterleukin-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