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

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

Research output: Contribution to journalArticle

100 Citations (Scopus)

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

Fingerprint

Muscle Cells
Calcium
Muscle
Messenger RNA
Proteins
Bradykinin
Pulmonary diseases
Chronic Obstructive Pulmonary Disease
Small Interfering RNA
Acetylcholine
Smooth Muscle Myocytes
Transfection
Smooth Muscle
Asthma
Western Blotting
Cytokines
Polymerase Chain Reaction
Genes
Chemical activation
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Pulmonary and Respiratory Medicine

Cite this

Role of transient receptor potential C3 in TNF-α-enhanced calcium influx in human airway myocytes. / White, Thomas A.; Xue, Ailing; Chini, Eduardo Nunes; Thompson, Michael; Sieck, Gary C; Wylam, Mark.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 35, No. 2, 08.2006, p. 243-251.

Research output: Contribution to journalArticle

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