Nicotine Reduces TNF-α Expression Through a α7 nAChR/MyD88/NF-ĸB Pathway in HBE16 Airway Epithelial Cells

Cellular Physiology and Biochemistry

关键词: Nicotine;    TNF-α;    Nicotine acetylcholine receptors;    MyD88;    NF-ŠB;   

DOI  :  10.1159/000329982

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Aims To explore the signaling mechanism associated with the inhibitory effect of nicotine on tumor necrosis factor (TNF)- α expression in human airway epithelial cells. Methods HBE16 airway epithelial cells were cultured and incubated with either nicotine or cigarette smoke extract (CE). Cells were then transfected with α1, α5, or α7 nicotinic acetylcholine receptor (nAChR)-specific small interfering RNAs (siRNAs). The effects of nicotine on the production of proinflammatory factors TNF-α, in transfected cells were analyzed. Furthermore, we assayed the expression levels of myeloid differentiation primary response gene 88 (MyD88) protein, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) p65 protein, NF-ĸB activity and NF-ĸB inhibitor alpha (I-ĸBα) expression in cells after treatment with nicotine or α7 nAChR inhibitor, α -bungarotoxin (α-BTX). Results The production of TNF-α was lower in cells pretreated with nicotine before lipopolysaccharide (LPS) stimulation, compared with LPS-only-treated cells. In contrast, in α7 siRNA-transfected cells incubated with nicotine and LPS, TNF-α expression was higher than that in non-transfected cells or in α1 or α5 siRNA-transfected cells. Addition of MyD88 siRNA or the NF-ĸB inhibitor pyridine-2,6-dithiocarboxylic acid (PDTC) also reduced TNF-α expression. Furthermore, we found that nicotine decreased MyD88 protein, NF-ĸB p65 protein, NF-ĸB activity and phospho-I-ĸBα expression induced by CE or LPS. The inhibitor α-BTX could reverse these effects. Conclusion Nicotine reduces TNF-α expression in HBE16 airway epithelial cells, mainly through an α7 nAChR/MyD88/NF-ĸB pathway.

【 授权许可】

CC BY-NC-ND