Brain-derived neurotrophic factor in TNF-α modulation of Ca 2+ in human airway smooth muscle

Y. S. Prakash, Michael A. Thompson, Christina M. Pabelick

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

There is increasing recognition that neurotrophin (NT) signaling occurs in non-neuronal tissues, including airway smooth muscle (ASM). We recently demonstrated that NTs, such as brain-derived neurotrophic factor (BDNF), enhance intracellular Ca2+ ([Ca2+]i) and force regulation in human ASM. Increased NT expression has been observed in airway diseases, such as asthma and allergy. In the present study, we tested the hypothesis that NTs contribute to inflammation-induced enhancement of ASM contractility. Using human ASM cells and real-time fluorescence [Ca 2+]i imaging, we examined the contribution of the high-affinity tropomyosin-related kinase and low-affinity, pan-NT p75NTR receptors to [Ca2+]i regulation under control conditions and after exposure to the proinflammatory cytokine TNF-α (20 ng/ml). Exposure to TNF-α enhanced [Ca2+]i responses to agonist (acetylcholine, histamine). Exposure to 10 nM BDNF for even 30 minutes substantially and synergistically enhanced TNF-α effects on [Ca 2+]i responses to agonist. Small interfering RNA suppression of tropomyosin-related kinase substantially blunted the effect of BDNF on [Ca2+]i responses to agonist (with greater effect on Ca2+ influx via store-operated Ca2+ entry compared with sarcoplasmic reticulum Ca2+ release) in both control and TNF-α-exposed cells. However, p75NTR suppression by small interfering RNA had no significant effect on [Ca2+]i responses in either cell group. These novel data demonstrate that NTs influence ASM contractility, and suggest a potential role for NTs in airway diseases.

Original languageEnglish (US)
Pages (from-to)603-611
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume41
Issue number5
DOIs
StatePublished - Nov 26 2009

Keywords

  • Capacitative calcium entry
  • Cytokine
  • Lung inflammation
  • Neurotrophin/tropomyosin-related kinase
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

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

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