Lin Chih-Yang, Lee Kun-Tsan, Lin Yen-You, Tsai Chun-Hao, Ko Chih-Yuan, Fong Yi-Chin, Hou Sheng-Mou, Chen Wei-Li, Huang Chien-Chung, Tang Chih-Hsin
Translational Medicine Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Department of Post-Baccalaureate Medicine, National Chung-Hsing University, Taichung, Taiwan; Department of Orthopedics, Taichung Veterans General Hospital, Taichung, Taiwan.
Int Immunopharmacol. 2024 Mar 30;130:111733. doi: 10.1016/j.intimp.2024.111733. Epub 2024 Feb 21.
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder in which monocytes adhering to synovial tissue differentiate into the pro-inflammatory M1 macrophage phenotype. Nerve growth factors (NGF) referred to as neurotrophins have been associated with inflammatory events; however, researchers have yet to elucidate the role of NGF in RA. Our examination of clinical tissue samples and analysis of data sourced from the Gene Expression Omnibus dataset unveiled elevated expression levels of M1 macrophage markers in human RA synovial tissue samples compared to normal tissue, with no such distinction observed for M2 markers. Furthermore, immunofluorescence data depicted increased expression levels of NGF and M1 macrophages in RA mice in contrast to normal mice. It appears that NGF stimulation facilitates macrophage polarization from the M0 to the M1 phenotype. It also appears that NGF promotes ICAM-1 production in human RA synovial fibroblasts, which enhances monocyte adhesion through the TrkA, MEK/ERK, and AP-1 signaling cascades. Our findings indicate NGF/TrkA axis as a novel target for the treatment of RA.
类风湿性关节炎（RA）是一种慢性自身免疫性炎症性疾病，其中粘附于滑膜组织的单核细胞分化为促炎性M1巨噬细胞表型。被称为神经营养因子的神经生长因子（NGF）与炎症事件有关；然而，研究人员尚未阐明NGF在RA中的作用。我们对临床组织样本的检查以及对来自基因表达综合数据集的数据的分析表明，与正常组织相比，人类RA滑膜组织样本中M1巨噬细胞标志物的表达水平升高，而M2标志物则没有这种差异。此外，免疫荧光数据显示，与正常小鼠相比，RA小鼠中NGF和M1巨噬细胞的表达水平增加。似乎NGF刺激促进巨噬细胞从M0表型向M1表型极化。似乎NGF还促进人RA滑膜成纤维细胞中ICAM-1的产生，这通过TrkA、MEK/ERK和AP-1信号级联增强单核细胞粘附。我们的研究结果表明，NGF/TrkA轴是治疗RA的新靶点。
