Li Sha, Zhou Bin, Liu Ben, Zhou Yaou, Zhang Huali, Li Tong, Zuo Xiaoxia
Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Department of Emergency, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Mol Med Rep. 2016 Dec;14(6):5057-5064. doi: 10.3892/mmr.2016.5904. Epub 2016 Oct 31.
Activation of the cholinergic anti-inflammatory pathway (CAP), which relies on the alpha-7 nicotinic acetylcholine receptor, has been reported to reduce proinflammatory cytokine levels in experimental arthritis. To gain more insight regarding the role of the CAP in the pathogenesis of arthritis, the present study focused on the modulation of macrophage infiltration. In a mouse model of collagen‑induced arthritis (CIA), nicotine and vagotomy were used to stimulate and inhibit the CAP, respectively. Subsequently, arthritic scores were measured and histopathological assessment of joint sections was conducted. Cluster of differentiation (CD)11b‑positive macrophages in the synovium were studied by immunofluorescence histochemistry. The serum levels of chemokines, including macrophage inflammatory protein (MIP)‑1α, monocyte chemoattractant protein (MCP)‑1 and MIP‑2 were evaluated by ELISA. Furthermore, the expression levels of C‑C chemokine receptor (CCR)2 and intercellular adhesion molecule (ICAM)‑1 in the synovium were evaluated by immunohistochemical staining. The results indicated that treatment with nicotine significantly attenuated the clinical and histopathological changes associated with arthritis, reduced CD11b‑positive macrophages in the synovium, and downregulated the serum expression levels of MIP‑1α and MCP‑1. Conversely, vagotomy aggravated arthritis and upregulated the expression levels of MCP‑1. However, MIP‑2 expression did not differ among the control, CIA, vagotomy and nicotine groups. In addition, the expression levels of CCR2 were reduced in the nicotine group; however, they were increased in the vagotomy group compared with in the untreated CIA group. The expression levels of ICAM‑1 in the synovium were also influenced by activation of the CAP. Taken together, the present results indicated that nicotine‑induced activation of the CAP in mice with CIA may reduce the number of macrophages in the synovium, which may serve a role in alleviating arthritis in mice.
据报道，依赖α-7烟碱型乙酰胆碱受体的胆碱能抗炎通路（CAP）的激活可降低实验性关节炎中促炎细胞因子水平。为了更深入了解CAP在关节炎发病机制中的作用，本研究聚焦于巨噬细胞浸润的调节。在胶原诱导性关节炎（CIA）小鼠模型中，分别使用尼古丁和迷走神经切断术来刺激和抑制CAP。随后，测量关节炎评分并对关节切片进行组织病理学评估。通过免疫荧光组织化学研究滑膜中分化簇（CD）11b阳性巨噬细胞。通过酶联免疫吸附测定法评估趋化因子的血清水平，包括巨噬细胞炎性蛋白（MIP）-1α、单核细胞趋化蛋白（MCP）-1和MIP-2。此外，通过免疫组织化学染色评估滑膜中C-C趋化因子受体（CCR）2和细胞间黏附分子（ICAM）-1的表达水平。结果表明，尼古丁治疗显著减轻了与关节炎相关的临床和组织病理学变化，减少了滑膜中CD11b阳性巨噬细胞，并下调了MIP-1α和MCP-1的血清表达水平。相反，迷走神经切断术加重了关节炎并上调了MCP-1的表达水平。然而，MIP-2表达在对照组、CIA组、迷走神经切断术组和尼古丁组之间没有差异。此外，尼古丁组中CCR2的表达水平降低；然而，与未治疗的CIA组相比，迷走神经切断术组中CCR2的表达水平升高。滑膜中ICAM-1的表达水平也受到CAP激活的影响。综上所述，目前的结果表明，尼古丁诱导的CIA小鼠中CAP的激活可能减少滑膜中巨噬细胞的数量，这可能在减轻小鼠关节炎中发挥作用。
