title: Attenuation of collagen induced arthritis via suppression on Th17 response by activating cholinergic anti-inflammatory pathway with nicotine.
abstract: The cholinergic anti-inflammatory pathway can inhibit the inflammation of collagen induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). However, the immunologic mechanisms that provide a therapeutic effect against the auto-inflammatory disease are not yet elucidated. The present study explores the effect of cholinergic anti-inflammatory pathway on CD4+ T cell responses in CIA. Forty DBA/1 mice were divided into 4 groups: a control group, a CIA group, a vagotomy group, and a nicotine group. The degree of arthritis was measured by arthritis score and hematoxylin and eosin. ELISA was used to detect the serum concentration of IFN-γ, IL-4 and IL-17A. Flow cytometry was used to detect the cytokines and transcription factors (TFs) (the TFs of Th1, Th2, and Th17 cells are T-bet, RORγτ and GATA3 respectively) in the spleen. Immunohistochemistry was used to analyze RORγτ expression in the joint synovium. Arthritis in the nicotine group was significantly lightened compared with that in the CIA group and in the vagotomy group. Nicotine attenuated Th17 lineage by reducing IL-17A production and RORγτ expression. The expressions of IL-4 and GATA3 were increased in the same setting. However, the expressions of IFN-γ and T-bet had no difference between the nicotine and the CIA group. Nicotine may induce a shift to the Th2 lineage and improve the Th1/Th2 imbalance. Activating the cholinergic anti-inflammatory pathway with nicotine can inhibit Th17 cell responses and may improve the Th1/Th2 imbalance in CIA, providing a new justification for its application in the treatment of rheumatoid arthritis.
authors.affiliation: Department of Rheumatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, People׳s Republic of China.
authors.forename: Shiyao
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Rheumatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, People׳s Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, People׳s Republic of China.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, People׳s Republic of China.
authors.forename: Huali
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, People׳s Republic of China. Electronic address: litonglltt@hotmail.com.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Rheumatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, People׳s Republic of China. Electronic address: susanzuo@hotmail.com.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Zuo
mesh_terms: D000818:Animals; D000843:Ankle Joint / Q000187:drug effects / Q000473:pathology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D050990:GATA3 Transcription Factor / Q000276:immunology; D008297:Male; D008811:Mice, Inbred DBA; D009538:Nicotine / Q000494:pharmacology* / Q000627:therapeutic use; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013583:Synovial Membrane / Q000187:drug effects / Q000276:immunology; D020825:T-Box Domain Proteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539901:Rorc protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D009538:Nicotine
keywords: Cholinergic anti-inflammatory pathway; Collagen induced arthritis; Nicotine; Rheumatoid arthritis; Th17 cell