Mechanisms of BDNF regulation in asthmatic airway smooth muscle

Bharathi Aravamudan, Michael A. Thompson, Christina M Pabelick, Y.s. Prakash

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Brainderived neurotrophic factor (BDNF), a neurotrophin produced by airway smooth muscle (ASM), enhances inflammation effects on airway contractility, supporting the idea that locally produced growth factors influence airway diseases such as asthma. We endeavored to dissect intrinsic mechanisms regulating endogenous, as well as inflammation (TNF-α)-induced BDNF secretion in ASM of nonasthmatic vs. asthmatic humans. We focused on specific Ca2+ regulationand inflammation-related signaling cascades and quantified BDNF secretion. We find that TNF-α enhances BDNF release by ASM cells, via several mechanisms relevant to asthma, including transient receptor potential channels TRPC3 and TRPC6 (but not TRPC1), ERK 1/2, PI3K, PLC, and PKC cascades, Rho kinase, and transcription factors cAMP response element binding protein and nuclear factor of activated T cells. Basal BDNF expression and secretion are elevated in asthmatic ASM and increase further with TNF-α exposure, involving many of these regulatory mechanisms. We conclude that airway BDNF secretion is regulated at multiple levels, providing a basis for autocrine effects of BDNF under conditions of inflammation and disease, with potential downstream influences on contractility and remodeling.

Original languageEnglish (US)
Pages (from-to)270-279
Number of pages10
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume311
Issue number2
DOIs
StatePublished - Aug 1 2016

Keywords

  • Airway
  • Asthma
  • Brain-derived neurotrophic factor
  • Inflammation
  • Neurotrophin
  • Secretion

ASJC Scopus subject areas

  • Physiology
  • Medicine(all)
  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology (medical)

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