Activation of the cholinergic anti-inflammatory system by nicotine attenuates arthritis via suppression of macrophage migration

Li,Sha; Zhou,Bin; Liu,Ben; Zhou,Yaou; Zhang,Huali; Li,Tong; Zuo,Xiaoxia

doi:10.3892/mmr.2016.5904

Activation of the cholinergic anti-inflammatory system by nicotine attenuates arthritis via suppression of macrophage migration

Authors:
- Sha Li
- Bin Zhou
- Ben Liu
- Yaou Zhou
- Huali Zhang
- Tong Li
- Xiaoxia Zuo
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Affiliations: 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, Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: October 31, 2016 https://doi.org/10.3892/mmr.2016.5904
Pages: 5057-5064
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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