Role of transient receptor potential C3 in TNF-α-enhanced calcium influx in human airway myocytes

Thomas A. White, Ailing Xue, Eduardo N. Chini, Michael Thompson, Gary C. Sieck, Mark E. Wylam

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

Previous studies have suggested that the proinflammatory cytokine, TNF-α, contributes to airway hyperresponsivness by altering airway smooth muscle (ASM) Ca2+ responses to agonist stimulation. The present study examined the effects of TNF-α on Ca2+ influx pathways in cultured human ASM cells (HASMCs). Proteins encoded by the transient receptor potential (TRP) gene family function as channels through which receptor-operated and store-operated Ca2+ entry (SOCE) occur. In the present study, the presence of TRPC1, TRPC3, TRPC4, TRPC5, and TRPC6 mRNA and protein expression was confirmed in cultured HASMCs using RT-PCR and Western blot analysis. TNF-α treatment significantly increased TRPC3 mRNA and protein levels in HASMCs as well as SOCE. TNF-α treatment also increased both the peak and plateau intracellular Ca2+ concentration responses in HASMCs elicited by acetylcholine and bradykinin. The effects of TNF-α treatment on SOCE and agonist-induced intracellular Ca2+ concentration responses were attenuated using small interfering RNA transfection, which knocked down TRPC3 expression. Thus, in inflammatory airway diseases, TNF-α treatment may result in increased myocyte activation due to altered Ca2+ influx pathways. These results suggest that TRPC3 may be an important therapeutic target in inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease.

Original languageEnglish (US)
Pages (from-to)243-251
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume35
Issue number2
DOIs
StatePublished - Aug 2006

Keywords

  • Human airway smooth muscle
  • Receptor-operated calcium entry
  • Store-operated calcium entry
  • TNF-α
  • Transient receptor potential channels

ASJC Scopus subject areas

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

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