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

P. Luo,T. Zhao,H. He

Published 2021 in Annals of the New York Academy of Sciences

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.

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