Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory for Oral Biomedical Engineering of Higher Education, and Stomatological Hospital of Chongqing Medical University, Chongqing, China.
Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory for Oral Biomedical Engineering of Higher Education, and Stomatological Hospital of Chongqing Medical University, Chongqing, China.
Int Immunopharmacol. 2024 May 30;133:112056. doi: 10.1016/j.intimp.2024.112056. Epub 2024 Apr 15.
The aim of this study was to investigate the effect of 4μ8c, an inhibitor targeting the endoplasmic reticulum stress-associated factor IRE1α, on macrophage polarization in an experimental model of diabetic periodontitis through ex vivo experiments.
Local alveolar bone parameters were evaluated using Micro-CT following intraperitoneal administration of 4μ8c in mice with experimental diabetic periodontitis. Surface markers indicating macrophage polarization were identified using immunofluorescence. In vitro experiments were performed employing bone marrow-derived macrophages and gingival fibroblasts. Macrophage polarization was determined using flow cytometry. Principal impacted signaling pathways were identified through Western blot analysis.
Results from both in vitro and in vivo experiments demonstrated that 4μ8c mitigated alveolar bone resorption and inflammation in mice with diabetic periodontitis. Furthermore, it modulated macrophage polarization towards the M2 phenotype and augmented M2 macrophage polarization through the MAPK signaling pathway.
These findings suggest that inhibiting IRE1α can modulate macrophage polarization and alleviate ligature-induced diabetic periodontitis via the MAPK signaling pathway. This unveils a novel mechanism, offering a scientific foundation for the treatment of experimental diabetic periodontitis.
本研究旨在通过体外实验，探讨内质网应激相关因子 IRE1α 抑制剂 4μ8c 对实验性糖尿病牙周炎中巨噬细胞极化的影响。
通过腹腔注射 4μ8c 后，采用 Micro-CT 评估实验性糖尿病牙周炎小鼠的局部牙槽骨参数。采用免疫荧光法鉴定表明巨噬细胞极化的表面标志物。体外实验采用骨髓来源的巨噬细胞和牙龈成纤维细胞进行。采用流式细胞术测定巨噬细胞极化。通过 Western blot 分析鉴定主要受影响的信号通路。
体外和体内实验结果均表明，4μ8c 减轻了糖尿病牙周炎小鼠的牙槽骨吸收和炎症。此外，它通过 MAPK 信号通路调节巨噬细胞向 M2 表型极化，并增强 M2 巨噬细胞极化。
这些发现表明，抑制 IRE1α 可通过 MAPK 信号通路调节巨噬细胞极化，缓解结扎诱导的糖尿病牙周炎。这揭示了一种新的机制，为实验性糖尿病牙周炎的治疗提供了科学依据。
