The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Department of Orthodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Ann N Y Acad Sci. 2022 Feb;1508(1):92-104. doi: 10.1111/nyas.14704. Epub 2021 Oct 20.
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.
最近，白细胞介素-38 (IL-38) 被鉴定为一种重要的抗炎和免疫抑制因子，但它在颞下颌关节 (TMJ) 炎症中的功能作用尚不清楚。本研究旨在阐明 IL-38 如何影响软骨细胞以及导致 TMJ 抗炎过程的潜在机制。Western blot、定量实时 PCR、酶联免疫吸附试验和免疫荧光分析用于验证 IL-38 对软骨细胞具有抗炎作用，并通过 Western blot 分析相关关键途径。使用 SiRNA-IL-38、siRNA-NLRP3 和 MCC950 来研究 IL-38 抗炎作用的机制。在体内研究中，通过在 TMJ 中注射完全弗氏佐剂诱导炎症模型，并使用小鼠重组 IL-38。组织学和免疫组织化学分析用于研究软骨的组织学变化。结果表明，IL-38 抑制了炎症细胞因子和 MMP 的表达。IL-38 通过抑制 MAPKs/NF-κB 和 NLRP3/caspase-1 途径来限制炎症。在体内，IL-38 减少了软骨细胞炎症并限制了软骨退化。本研究首次表明，IL-38 在 TMJ 软骨中发挥保护作用。IL-38 通过 NLRP3/caspase-1 途径发挥抗炎作用，可能是治疗 TMJ 炎症的有前途的药物。
