IL‐38–mediated NLRP3/caspase‐1 inhibition is a disease‐modifying treatment for TMJ inflammation

Abstract

Recently, interleukin-38 (IL-38) was identified as an important anti-inflammatory and immunosuppressive factor, but its functional role in temporomandibular joint (TMJ) inflammation remains unknown. This study aimed to elucidate how IL-38 affects chondrocytes and the underlying mechanism that contributes to anti-inflammatory processes in the TMJ. Western blotting, quantitative real-time PCR, enzyme-linked immunosorbent assay, and immunofluorescence analysis were used to verify that IL-38 has anti-inflammatory effects on chondrocytes, and the related key pathways were analyzed by western blotting. SiRNA-IL-38, siRNA-NLRP3, and MCC950 were used to investigate the mechanism underlying the anti-inflammatory effects of IL-38. Inflammation models were induced by injection of complete Freund's adjuvant in TMJ with mouse recombinant IL-38 in in vivo studies. Histological and immunohistochemical analyses were used to investigate histological changes in the cartilage. The results showed that IL-38 inhibited the expression of inflammatory cytokines and MMPs. IL-38 limited inflammation by inhibiting the expression of MAPKs/NF-κB and the NLRP3/caspase-1 pathway. In vivo, IL-38 reduced chondrocyte inflammation and limited cartilage degeneration. This study shows for the first time that IL-38 plays a protective role in TMJ cartilage. IL-38 exerts anti-inflammatory effects through the NLRP3/caspase-1 pathway and may be a promising agent for treating TMJ inflammation.