State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.; Department of Orthodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Int Immunopharmacol. 2023 Sep;122:110619. doi: 10.1016/j.intimp.2023.110619. Epub 2023 Jul 17.
Interleukin (IL)-38 was discovered as an anti-inflammatory factor. However, IL-38's role in M1 macrophage polarization in the temporomandibular joint (TMJ) and the related mechanism are still unclear. We aimed to explore the effect and the mechanism of IL-38 on synovial inflammation in the TMJ in this study.
The expression of IL-38 in the TMJ synovium and macrophages was determined using immunohistochemistry (IHC) and Western blotting (WB). M1 macrophage polarization was induced by LPS, the macrophages were pre-treated with IL-38, and the levels of inflammatory markers associated with M1 macrophages were measured. To assess the mechanism of IL-38, small-interfering RNA (siRNA)-GLUT-1 and STF31 were administered to macrophages, and the affected pathways were identified by WB. The effect of macrophage-conditioned medium (CM) on chondrocyte function was also determined. Finally, a mouse model of CFA-induced TMJ inflammation was established. Histological staining and IHC were used to determine the effect of IL-38.
IL-38 was detected at high levels in macrophages after lipopolysaccharide (LPS)challenge, and IL-38 downregulated M1 macrophage-related proinflammatory markers (iNOS, IL-6, TNF-α, and COX-2) in vitro. IL-38 suppressed M1 polarization by inhibiting GLUT-1 expression, NF-κB signaling, and MAPK signaling. Intriguingly, CM from macrophages that were pretreated with IL-38 and STF31 decreased inflammatory protein expression in chondrocytes. In addition, intra-articular injection of recombinant IL-38 ameliorated synovial inflammation in the TMJ by inhibiting M1 macrophage polarization and suppressing cartilage inflammation in vivo.
IL-38 is a novel anti-inflammatory factor that contributes to alleviating TMJ inflammation by inhibiting macrophage M1 polarization, thereby ameliorating chondrocyte inflammation and restoring TMJ homeostasis.
白细胞介素（IL）-38 被发现是一种抗炎因子。然而，IL-38 在颞下颌关节（TMJ）中 M1 巨噬细胞极化中的作用及其相关机制尚不清楚。本研究旨在探讨 IL-38 对 TMJ 滑膜炎症的影响及其机制。
采用免疫组织化学（IHC）和 Western blot（WB）检测 TMJ 滑膜组织和巨噬细胞中 IL-38 的表达。用 LPS 诱导 M1 巨噬细胞极化，用 IL-38 预处理巨噬细胞，检测与 M1 巨噬细胞相关的炎症标志物水平。为了评估 IL-38 的作用机制，用小干扰 RNA（siRNA）-GLUT-1 和 STF31 处理巨噬细胞，通过 WB 鉴定受影响的途径。还测定了巨噬细胞条件培养基（CM）对软骨细胞功能的影响。最后，建立 CFA 诱导的 TMJ 炎症小鼠模型，用组织学染色和 IHC 检测 IL-38 的作用。
脂多糖（LPS）刺激后，巨噬细胞中 IL-38 表达水平升高，体外 IL-38 下调 M1 巨噬细胞相关促炎标志物（iNOS、IL-6、TNF-α 和 COX-2）。IL-38 通过抑制 GLUT-1 表达、NF-κB 信号和 MAPK 信号抑制 M1 极化。有趣的是，用 IL-38 和 STF31 预处理的巨噬细胞 CM 降低了软骨细胞中炎症蛋白的表达。此外，关节内注射重组 IL-38 通过抑制 M1 巨噬细胞极化和抑制体内软骨炎症，改善 TMJ 滑膜炎症。
IL-38 是一种新型抗炎因子，通过抑制巨噬细胞 M1 极化缓解 TMJ 炎症，从而改善软骨细胞炎症并恢复 TMJ 稳态。
