IL-36α: a novel cytokine involved in the catabolic and inflammatory response in chondrocytes

Recent studies confer to IL-36 alpha pro-inflammatory properties. However, little is known about the expression and function of IL-36 alpha in cartilage. This study sought to analyze the expression of IL-36 alpha in healthy and OA cartilage. Next, we determined the effects of recombinant IL-36 alpha on catabolism and inflammation in chondrocytes. For completeness, part of the signaling pathway elicited by IL-36 alpha was also explored. IL-36 alpha expression was evaluated by immunohistochemistry and RT-qPCR. Expression of MMP-13, NOS2 and COX-2 was also determined in OA articular chondrocytes treated with recombinant IL-36 alpha. I kappa B-alpha and P-p38 was explored by western blot. We observed a low constitutive expression of IL-36 alpha in healthy human chondrocytes. However, OA chondrocytes likely expressed more IL-36 alpha than healthy chondrocytes. In addition, immune cells infiltrated into the joint and PBMCs express higher levels of IL-36 alpha in comparison to chondrocytes. OA chondrocytes, treated with IL-36 alpha, showed significant increase in the expression of MMP-13, NOS2 and COX-2. Finally, IL-36 alpha stimulated cells showed NF kappa B and p38 MAPK activated pathways. IL-36 alpha acts as a pro-inflammatory cytokine at cartilage level, by increasing the expression of markers of inflammation and cartilage catabolism. Like other members of IL-1 family, IL-36 alpha acts through the activation of NF kappa B and p38 MAPK pathway.