The inflammatory regulation of TRPA1 expression in human A549 lung epithelial cells

Samu Luostarinen, Mari Hämäläinen, Noriyuki Hatano, Katsuhiko Muraki, Eeva Moilanen

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Abstract

Transient receptor potential ankyrin-1 (TRPA1) is an ion channel mediating pain and cough signals in sensory neurons. We and others have shown that TRPA1 is also expressed in some non-neuronal cells and supports inflammatory responses. To address the pathogenesis and to uncover potential targets for pharmacotherapy in inflammatory lung diseases, we set out to study the expression of TRPA1 in human A549 lung epithelial cells under inflammatory conditions. TRPA1 expression was determined by RT-qPCR and Western blotting at a mRNA and protein level, respectively and its function was studied by Fluo 3-AM intracellular Ca2+ measurement in A549 lung epithelial cells. TRPA1 promoter activity was assessed by reporter gene assay. TRPA1 expression was very low in A549 cells in the absence of inflammatory stimuli. Tumor necrosis factor-α (TNF-α) significantly increased TRPA1 expression and a synergy was found between TNF-α, interleukin-1β (IL-1β) and interferon-γ (IFN-γ). Reporter gene experiments indicate that the combination of TNF-α and IL-1β increases TRPA1 promoter activity while the effect of IFN-γ seems to be non-transcriptional. Interestingly, the glucocorticoid dexamethasone downregulated TRPA1 expression in A549 cells by reducing TRPA1 mRNA stability in a transcription-dependent manner. Furthermore, pharmacological blockade of TRPA1 reduced the production of the pro-inflammatory cytokine IL-8. In conclusion, TRPA1 was found to be expressed and functional in human A549 lung epithelial cells under inflammatory conditions. The anti-inflammatory steroid dexamethasone reduced TRPA1 expression through post-transcriptional mechanisms. The results reveal TRPA1 as a potential mediator and drug target in inflammatory lung conditions.

Original languageEnglish
Article number102059
JournalPulmonary Pharmacology and Therapeutics
Volume70
DOIs
Publication statusPublished - 2021
Publication typeA1 Journal article-refereed

Keywords

  • Glucocorticoids
  • Inflammation
  • Interferon-gamma (IFN-γ)
  • Interleukin-1beta (IL-1β)
  • Transient receptor potential ankyrin 1 (TRPA1) cation channel
  • Tumor necrosis factor-alpha (TNF-α)

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Biochemistry, medical
  • Pharmacology (medical)

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