Early response genes induced in chondrocytes stimulated with the inflammatory cytokine interleukin-1 beta

Recent work has established that IL-1 beta plays a central role in the infl ammation and connective tissue destruction observed in both rheumatoid arth ritis and osteoarthritis. These processes result from the ability of this i nflammatory cytokine to activate expression of genes for neutral proteases, such as the matrix metalloproteinases. While IL-1 beta activates matrix me talloproteinase genes within several hours, it also activates immediate ear ly genes, which are required for the later expression of matrix metalloprot einases and other arthritis-perpetuating genes, are also activated. To iden tify putative immediate early genes involved in IL-1 beta -mediated arthrit ic disease, a chondrocytic cell line (SW1353) was stimulated with this cyto kine for 2 hours, total RNA was isolated, and expressed genes were identifi ed by microarray analysis. This analysis identified alterations in the expr ession of multiple transcription factors, cytokines, growth factors and the ir receptors, adhesion molecules, proteases, and signaling intermediates th at may contribute to inflammation and cartilage destruction in arthritis. I nterestingly, confirmation of the expression of activating protein-1 family members by reverse transcriptase polymerase chain reaction revealed a pref erential increase in junB, a known transcriptional antagonist of c-jun. The failure to observe induction of early growth response gene-1, which was de tected by reverse transcriptase polymerase chain reaction to be substantial ly and transiently induced by 1 hour of IL-1 treatment, may be explained by the known instability of the message after early induction. However, this analysis has identified numerous IL-1 beta -responsive genes that warrant f urther investigation as mediators of disease in arthritis.