IL-38-mediated NLRP3/caspase-1 inhibition is a disease-modifying treatment for TMJ inflammation
IL-38-mediated NLRP3/caspase-1 inhibition is a disease-modifying treatment for TMJ inflammation
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DOI：
10.1111/nyas.14704
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发表时间：
2021-10-20
影响因子：
5.2
通讯作者：
He, Hong
中科院分区：
文献类型：
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作者：
Luo, Ping;Zhao, Tingting;He, Hong
近年来，白细胞介素-38（IL-38）被认为是一种重要的抗炎和免疫抑制因子，但其在颞下颌关节（TMJ）炎症中的作用尚不清楚。本研究旨在阐明IL-38如何影响软骨细胞以及有助于TMJ抗炎过程的潜在机制。采用Western blotting、实时荧光定量PCR、酶联免疫吸附试验和免疫荧光分析等方法验证IL-38对软骨细胞的抗炎作用，并通过Western blotting分析相关的关键通路。使用SiRNA-IL-38、siRNA-NLRP 3和MCC 950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和小鼠重组IL-38来诱导炎症模型。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可抑制炎性细胞因子和MMPs的表达。IL-38通过抑制MAPK/NF-κ B和NLRP 3/caspase-1通路的表达来限制炎症。在体内，IL-38减少软骨细胞炎症和有限的软骨变性。这项研究首次表明IL-38在TMJ软骨中起保护作用。IL-38通过NLRP 3/caspase-1通路发挥抗炎作用，可能是治疗TMJ炎症的有前途的药物。
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-kappa B 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.