Gui Huan, Tong Qiang, Qu Wenchun, Mao Chen-Mei, Dai Sheng-Ming
Department of Pharmacy, Children's Hospital of Soochow University, Suzhou, China; Department of Rheumatology & Immunology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Department of Rheumatology & Immunology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Int Immunopharmacol. 2015 May;26(1):86-91. doi: 10.1016/j.intimp.2015.03.006. Epub 2015 Mar 16.
Since the discovery of the endogenous receptor for Δ(9)-tetrahydrocannabinol, a main constituent of marijuana, the endocannabinoid system (comprising cannabinoid receptors and their endogenous ligands, as well as the enzymes involved in their metabolic processes) has been implicated as having multiple regulatory functions in many central and peripheral conditions, including rheumatoid arthritis (RA). RA is an immune-mediated inflammatory disease that is associated with the involvement of many kinds of cells (such as fibroblastlike synoviocytes [FLSs], osteoclasts, T cells, B cells, and macrophages) and molecules (such as interleukin-1β, tumor necrosis factor-α, interleukin-6, matrix metalloproteinases [MMPs], and chemokines). Increasing evidence suggests that the endocannabinoid system, especially cannabinoid receptor 2 (CB2), has an important role in the pathophysiology of RA. Many members of the endocannabinoid system are reported to inhibit synovial inflammation, hyperplasia, and cartilage destruction in RA. In particular, specific activation of CB2 may relieve RA by inhibiting not only the production of autoantibodies, proinflammatory cytokines, and MMPs, but also bone erosion, immune response mediated by T cells, and the proliferation of FLSs. In this review, we will discuss the possible functions of the endocannabinoid system in the modulation of RA, which may be a potential target for treatment.
自从发现大麻的主要成分Δ(9)-四氢大麻酚的内源性受体以来，内源性大麻素系统（由大麻素受体及其内源性配体以及参与其代谢过程的酶组成）已被认为在包括类风湿性关节炎（RA）在内的许多中枢和外周疾病中具有多种调节功能。RA是一种免疫介导的炎症性疾病，与多种细胞（如成纤维样滑膜细胞[FLS]、破骨细胞、T细胞、B细胞和巨噬细胞）和分子（如白细胞介素-1β、肿瘤坏死因子-α、白细胞介素-6、基质金属蛋白酶[MMP]和趋化因子）的参与有关。越来越多的证据表明，内源性大麻素系统，尤其是大麻素受体2（CB2），在RA的病理生理学中起重要作用。据报道，内源性大麻素系统的许多成员可抑制RA中的滑膜炎症、增生和软骨破坏。特别是，CB2的特异性激活可能通过不仅抑制自身抗体、促炎细胞因子和MMP的产生，而且抑制骨侵蚀、T细胞介导的免疫反应和FLS的增殖来缓解RA。在这篇综述中，我们将讨论内源性大麻素系统在调节RA中的可能功能，这可能是一个潜在的治疗靶点。
