Brain-derived neurotrophic factor in cigarette smoke-induced airway hyperreactivity

Venkatachalem Sathish, Sarah Kay VanOosten, Brent S. Miller, Bharathi Aravamudan, Michael A. Thompson, Christina M. Pabelick, Robert Vassallo, Y. S. Prakash

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Enhanced airway smooth muscle (ASM) contractility contributes to increased resistance to airflow in diseases such as bronchitis and asthmathat occur in passive smokersexposedto secondhandsmoke. Little information exists on the cellular mechanisms underlying such airway hyperreactivity. Sputum samples of patients with chronic sinusitis, bronchitis, and asthma show increased concentrations of growth factors called neurotrophins, including brain-derived growth factor (BDNF), but their physiological significance remains unknown. In human ASM, we tested the hypothesis that BDNF contributes to increased contractility with cigarette smoke exposure. The exposure of ASM to 1% or 2% cigarette smoke extract (CSE) for 24 hours increased intracellular calcium ([Ca2+]i) responses to histamine, and further potentiated the enhancing effects of a range of BDNF concentrations on such histamine responses. CSE exposure increased the expression of the both high-affinity and lowaffinity neurotrophin receptors tropomyosin-related kinase (Trk)-B and p75 pan-neurotrophin receptor, respectively. Quantitative ELISA showedthatCSEincreasedBDNFsecretionbyhumanASMcells.BDNF small interfering (si)RNA and/or the chelation of extracellular BDNF, using TrkB-fragment crystallizable, blunted the effects of CSE on [Ca2+]i responses aswell as the CSE enhancement of cell proliferation, whereas TrkB siRNA blunted the effects of CSE on ASM contractility. These data suggest that cigarette smoke is a potent inducer of BDNF and TrkB expression and signaling in ASM, which then contribute to cigarette smoke-induced airway hyperresponsiveness.

Original languageEnglish (US)
Pages (from-to)431-438
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume48
Issue number4
DOIs
StatePublished - Apr 2013

Keywords

  • Asthma
  • Environmental tobacco exposure
  • Neurotrophin
  • Secondhand smoke
  • TrkB

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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