Peer-Reviewed Journal Details
Mandatory Fields
McDermott BT;Peffers MJ;McDonagh B;Tew SR;
2019
July
Journal Of Biological Chemistry
Translational regulation contributes to the secretory response of chondrocytic cells following exposure to Interleukin-1.
Published
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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 translational capacity during osteoarthritis, but a study of how disease relevant signals affect chondrocyte proteintranslation at the transcriptomic level has not previously been performed. In this study we describe how the inflammatory cytokine interleukin 1-beta (IL-1) rapidly affects protein translation in the chondrocytic cell line SW1353. Using ribosome profiling we demonstrate that IL-1 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 changes in an number of the proteins which were differentially translated.Translationally-regulated secreted proteins included a number of chemokines and cytokines, underlining the rapid, translationally-mediated inflammatory cascade that is initiated by IL-1. Although fewer cellular proteins were found to be regulated in both ribosome profiling and proteomic datasets, we did find increased levels of SOD2, indicative of redox changes within SW1353 cells being modulated at the translational level. In conclusion, we have produced combined ribosome profiling and proteomic datasets which provide a valuable resource in understanding the processes that are occurring during cytokine stimulation of chondrocytic cells.
1083-351X
10.1074/jbc.RA118.006865
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