Nicotine inhibits tumor necrosis factor-α induced IL-6 and IL-8 secretion in fibroblast-like synoviocytes from patients with rheumatoid arthritis.
It was recently demonstrated that the cholinergic anti-inflammatory pathway can modulate host inflammatory responses via cholinergic mediators or via electrical stimulation of the vagus nerve. Here, we investigated whether nicotine, a selective cholinergic agonist, plays any anti-inflammatory role in rheumatoid arthritis fibroblast-like synoviocytes (FLS). We observed that low concentrations (0.1-100 μM) of nicotine did not affect FLS viability in lactate dehydrogenase release test or the MTT assay. Nicotine at concentrations of 0.1-10 μM dose reduced the protein and mRNA expression of IL-6 and IL-8 induced by tumor necrosis factor-α (TNFα). Nicotine also inhibited nuclear factor (NF)-κB (p65) translocation from the cytoplasm to the nucleus, based on Western blotting and immunocytochemical analysis. In conclusion, nicotine can inhibit the TNFα dependant inflammatory pathway in synoviocytes by suppressing the activation of the NF-κB pathway.
Zhou
Yaou
Y
Department of Rheumatology and Clinical Immunology, Xiangya Hospital, Central South University, 110 Xiangya Road, 410008 Changsha, Hunan, China.
Zuo
Xiaoxia
X
Li
Yisha
Y
Wang
Yanping
Y
Zhao
Hongjun
H
Xiao
Xianzhong
X
D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009538:Nicotine