Neuropeptides and capsaicin stimulate the release of inflammatory cytokines in a human bronchial epithelial cell line

Neuropeptides. 1999 Dec;33(6):447-56. doi: 10.1054/npep.1999.0761.


The role of neuropeptides in initiating and modulating airway inflammation was examined in a human bronchial epithelial cell line (i.e. BEAS-2B). At a range of concentrations, exposure of BEAS-2B cells to Substance P (SP) or calcitonin gene related protein resulted in immediate increases in intracellular calcium ([Ca(2+)](i)), the synthesis of the transcripts for the inflammatory cytokines, IL-6, IL-8 and TNFalpha after 2 h exposure, and the release of their proteins after 6 h exposure. Addition of thiorphan (100 nM), an inhibitor of neutral endopeptidase, enhanced the levels of SP-stimulated cytokine release. Stimulation of IL-6 by SP occurred in a conventional receptor-mediated manner as demonstrated by its differential release by fragments SP 4-11 and SP 1-4 and by the blockage of IL-6 release with the non-peptide, NK-1 receptor antagonist, CP-99 994. In addition to the direct stimulation of inflammatory cytokines, SP (0.5 microM), in combination with TNFalpha (25 units/ml), synergistically stimulated IL-6 release. BEAS-2B cells also responded to the botanical irritant, capsaicin (10 microM) with increases in [Ca(2+)](i) and IL-8 cytokine release after 4 h exposure. The IL-8 release was dependent on the presence of extracellular calcium. Capsaicin-stimulated increases of [Ca(2+)](i) and cytokine release could be reduced to control levels by pre-exposure to capsazepine, an antagonist of capsaicin (i.e. vanilloid) receptor(s) or by deletion of extracellular calcium from the exposure media. The present data indicate that the BEAS-2B human epithelial cell line expresses neuropeptide and capsaicin-sensitive pathways, whose activation results in immediate increases of [Ca(2+)](i) stimulation of inflammatory cytokine transcripts and the release of their cytokine proteins.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bronchi / cytology
  • Calcitonin Gene-Related Peptide / pharmacology*
  • Calcium / metabolism
  • Capsaicin / pharmacology*
  • Cell Line, Transformed
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Gene Expression / immunology
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / immunology
  • Interleukin-8 / metabolism
  • Peptide Fragments / pharmacology*
  • Piperidines / pharmacology
  • Protease Inhibitors / pharmacology
  • RNA, Messenger / analysis
  • Substance P / pharmacology*
  • Thiorphan / pharmacology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • Interleukin-6
  • Interleukin-8
  • Peptide Fragments
  • Piperidines
  • Protease Inhibitors
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • 3-(2-methoxybenzylamino)-2-phenylpiperidine
  • Substance P
  • substance P (4-11)
  • substance P (1-4)
  • Thiorphan
  • Calcitonin Gene-Related Peptide
  • Capsaicin
  • Calcium