NLRC5 attenuates inflammatory response in IL-113-stimulated human osteoarthritis chondrocytes through the NF-κB signaling pathway

NOD-like receptor family caspase recruitment domain family domain containing 5 (NLRC5) has been found to be a critical mediator of inflammatory response. However, the role of NLRC5 in osteoarthritis (OA) has not been reported. Our results showed that NLRC5 was down-regulated by IL-1 beta induction in chondrocytes. Overexpression of NLRC5 in chondrocytes significantly suppressed IL-1 beta-induced inflammatory response through inhibiting the production of multiple inflammatory mediators including inducible nitric oxide synthases (iNOS), and cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), NO, TNF-alpha and IL-6, as well matrix metalloproteinase 3 (MMP-3) and MMP-13. Consistently, NLRC5 knockdown exhibited opposite effects on the production of these inflammatory mediators in IL-1 beta-induced chondrocytes. Furthermore, overexpression of NLRC5 increased the I kappa B alpha expression, while decreased the p-p65 expression, indicating that NLRC5 inhibited the activation of NF-kappa B signaling. Additionally, inhibition of NF-kappa B by PDTC mitigated the si-NLRC5-mediated promotion of IL-1 beta-induced inflammatory injury in chondrocytes. Finally, NLRC5 treatment ameliorated cartilage degeneration in an OA model in rats. Taken together, these findings revealed that NLRC5 attenuated IL-1 beta-induced inflammatory injury in chondrocytes through regulating the NF-kappa B signaling.