title: Activation of the cholinergic anti-inflammatory system by nicotine attenuates arthritis via suppression of macrophage migration.
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.
authors.affiliation: Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Emergency, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Ben
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yaou
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Huali
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Zuo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology*; D018932:Chemokine CCL2 / Q000097:blood / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D010641:Phenotype; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D018925:Chemokines; D018799:Intercellular Adhesion Molecule-1; D009538:Nicotine