Autocrine Acetylcholine, Induced by IL-17A via NFκB and ERK1/2 Pathway Activation, Promotes MUC5AC and IL-8 Synthesis in Bronchial Epithelial Cells

Mediators Inflamm. 2016:2016:9063842. doi: 10.1155/2016/9063842. Epub 2016 May 19.

Abstract

IL-17A is overexpressed in the lung during acute neutrophilic inflammation. Acetylcholine (ACh) increases IL-8 and Muc5AC production in airway epithelial cells. We aimed to characterize the involvement of nonneuronal components of cholinergic system on IL-8 and Muc5AC production in bronchial epithelial cells stimulated with IL-17A. Bronchial epithelial cells were stimulated with recombinant human IL-17A (rhIL-17A) to evaluate the ChAT expression, the ACh binding and production, the IL-8 release, and the Muc5AC production. Furthermore, the effectiveness of PD098,059 (inhibitor of MAPKK activation), Bay11-7082 (inhibitor of IkBα phosphorylation), Hemicholinium-3 (HCh-3) (choline uptake blocker), and Tiotropium bromide (Spiriva®) (anticholinergic drug) was tested in our in vitro model. We showed that rhIL-17A increased the expression of ChAT, the levels of ACh binding and production, and the IL-8 and Muc5AC production in stimulated bronchial epithelial cells compared with untreated cells. The pretreatment of the cells with PD098,059 and Bay11-7082 decreased the ChAT expression and the ACh production/binding, while HCh-3 and Tiotropium decreased the IL-8 and Muc5AC synthesis in bronchial epithelial cells stimulated with rhIL-17A. IL-17A is involved in the IL-8 and Muc5AC production promoting, via NFκB and ERK1/2 pathway activation, the synthesis of ChAT, and the related activity of autocrine ACh in bronchial epithelial cells.

MeSH terms

  • Acetylcholine / metabolism*
  • Autocrine Communication / drug effects
  • Bronchi / cytology
  • Cell Line
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism*
  • Flow Cytometry
  • Humans
  • Interleukin-17 / pharmacology*
  • Interleukin-8 / metabolism*
  • MAP Kinase Signaling System / drug effects
  • Mucin 5AC / metabolism*
  • NF-kappa B / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Interleukin-17
  • Interleukin-8
  • MUC5AC protein, human
  • Mucin 5AC
  • NF-kappa B
  • Acetylcholine