NLRC5 attenuates inflammatory response in IL-1β-stimulated human osteoarthritis chondrocytes through the NF-κB signaling pathway.

Yiping Mu,Jie Wu,Yang Zhang,Qi Li

doi:10.18632/aging.203453

Abstract

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-1β induction in chondrocytes. Overexpression of NLRC5 in chondrocytes significantly suppressed IL-1β-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-α 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-1β-induced chondrocytes. Furthermore, overexpression of NLRC5 increased the IĸBα expression, while decreased the p-p65 expression, indicating that NLRC5 inhibited the activation of NF-κB signaling. Additionally, inhibition of NF-κB by PDTC mitigated the si-NLRC5-mediated promotion of IL-1β-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-1β-induced inflammatory injury in chondrocytes through regulating the NF-κB signaling.

Highlights

Osteoarthritis (OA) was considered as a prototypical arthropathy, which is irrelevant to inflammation [1–3]
NLRC5 treatment ameliorated cartilage degeneration in an OA model in rats. These findings revealed that NLRC5 attenuated IL-1β-induced inflammatory injury in chondrocytes through regulating the NF-κB signaling
NLRC5 expression was down-regulated in IL-1βinduced chondrocytes

Summary

INTRODUCTION

Osteoarthritis (OA) was considered as a prototypical arthropathy, which is irrelevant to inflammation [1–3]. The mechanism of OA is quite complex, many cell types such as articular chondrocytes, synovial cells, and other cells of diarthrodial joints, are involved in OA development [1]. These cells express inflammatory mediators, pro-inflammatory cytokines, and matrix degrading enzymes, which are crucial molecules for the progression of OA in synovial joints [4, 5]. NLRC5 inhibits the activation of NF-κB signaling induced by LPS, TNF-α or IL-1β [16]. Based on these evidences, www.aging-us.com we speculated that NLRC5 may be involved in the pathogenesis of OA. The potential roles of NLRC5 in chondrocytes was investigated and the underlying mechanism was explored

MATERIALS AND METHODS

RESULTS

DISCUSSION