title: Regulatory effect of nicotine on collagen-induced arthritis and on the induction and function of in vitro-cultured Th17 cells.
abstract: OBJECTIVE
  To determine the effect of nicotine stimulation on collagen-induced arthritis (CIA), especially on Th17 cells, and the influence of activated acetylcholine receptor signaling on the induction and function of in vitro-cultured Th17 cells.
  
  
  METHODS
  Mice were divided into control and experimental (nicotine) group, and PBS or nicotine-PBS was orally administered from Day 21 to Day 28. Phenotypic changes in spleen CD4(+) cells were measured by flow cytometry. α7nAChR expression in Th17 cells was detected using flow cytometry, western blotting and real-time PCR. Purified Th17 cells were further stimulated with nicotine. The cytometric bead array (CBA) assay was employed to measure TNF-α levels in mice serum and IL-17A levels in the supernatants of nicotine-treated cell cultures.
  
  
  RESULTS
  Compared with their counterparts, mice receiving oral nicotine showed a delayed progress of arthritis and more attenuated signs of histological changes. Moreover, serum TNFα levels were lower in the nicotine-treated group. Spleen IL-17 level of nicotine-treated mice was lower than that of the control group, and the mRNA expression of pro-inflammatory cytokines (IL-17A and IL-6) in splenocytes were also lower than that of the control group. α7nAChR expression was detected on in vitro-cultured IL-17A(+) cells. Cells treated with 10 (- 6) M nicotine expressed lower IL-17A levels. Similarly, supernatants from nicotine-treated cell cultures also showed lower IL-17A levels.
  
  
  CONCLUSIONS
  Nicotine stimulation attenuated signs and severity of arthritis in mice. Activation of nicotine acetylcholine receptors on in vitro-cultured Th17 cells decreased their pro-inflammatory function, which may play a potential role in alleviating arthritis in mice.
authors: Blood Engineering Laboratory, Shanghai Blood Center , Shanghai , P. R. China.
authors: Yiming
authors: Y
authors: Yang
authors: Yan
authors: Y
authors: Yang
authors: Jie
authors: J
authors: Yang
authors: Rufeng
authors: R
authors: Xie
authors: Yana
authors: Y
authors: Ren
authors: Huahua
authors: H
authors: Fan
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy*; D002478:Cells, Cultured; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D009538:Nicotine / Q000494:pharmacology* / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D020381:Interleukin-17; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009538:Nicotine
keywords: Acetylcholine receptors; CD4+IL-17A+Th17 cells; Collagen-induced arthritis