Ribosome profiling of chondrocytic cell line SW1353 following exposure to IL-1B

Osteoarthritis is a chronic disease characterised by the loss of articular cartilage in synovial joints through a process of extracellular matrix destruction that is strongly associated with inflammatory stimuli. Chondrocytes undergo changes to their protein translation capacity during osteoarthritis, but a study of how disease-relevant signals effect chondrocyte protein translation at the transcriptomic level has not previously been performed. In this study we describe how the inflammatory cytokine interleukin 1-beta (IL-1β) rapidly affects protein translation in the chondrocytic cell line SW1353. Using ribosome profiling we demonstrate that IL-1β induced altered translation of inflammatory-associated transcripts such as NFKB1, TNFAIP2, MMP13, CCL2 and CCL7, as well as a number of ribosome-associated transcripts, through differential translation and the use of multiple open reading frames. Proteomic analysis of the cellular layer and the conditioned media of these cells identified that proteins which were differentially translated were most readily detected in the secretome. These translationally regulated secreted proteins included a number of chemokines and cytokines, underlining the rapid, translationally-mediated inflammatory cascade that is initiated by IL-1 β.