ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2023
The regulation of TRPA1 expression and function by Th1 and Th2-type inflammation in human A549 lung epithelial cells.
Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 20 citations in OpenAlex.
- Angiotensin (1-7) improves diabetes mellitus-induced erectile dysfunction in rats by modulating the Cav-1/eNOS signaling pathway.Sexual medicine · 2026Article
- TRPA1 Regulates Fibrosis-Associated Transcriptional Pathways in Human Lung Epithelial Cells.Basic & clinical pharmacology & toxicology · 2026Article
- Sepsis-associated acute lung injury: do inflammatory lipid mediators flood the lungs by activating pulmonary TRP channels?Intensive care medicine experimental · 2026Review
- Review
- Transient receptor potential ankyrin 1 promotes the expression of interferon-stimulated antiviral genes in human A549 lung epithelial cells.Molecular pharmacology · 2026Article
- Bioinformatic prediction of key genes involved in pro-chondrogenic effect of fragmentated cartilage transplantation.Scientific reports · 2025Article
- Is the SPLUNC1-Orai1 axis a critical determinant of lung health?Biochemical Society transactions · 2025Review
- The Contact Allergen Methylisothiazolinone (MIT) is a Potent Activator of the TRPA1 Ion Channel.Pharmacology research & perspectives · 2025Article
- Profiling human iPSC-derived sensory neurons for analgesic drug screening using a multi-electrode array.Cell reports methods · 2025Article
- Association of diurnal temperature range and childhood asthma: a population-based cross-sectional study in a Tropical City, China.BMC public health · 2025Article
- Mast Cells at the Crossroads of Hypersensitivity Reactions and Neurogenic Inflammation.International journal of molecular sciences · 2025Review
- Modulating TRPV1 and TRPA1 channels: a viable strategy for treating asthma using Chinese herbal medicines.Frontiers in pharmacology · 2025Review
- Calcium Signaling in Airway Epithelial Cells: Current Understanding and Implications for Inflammatory Airway Disease.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Dual role of transient receptor potential ankyrin 1 in respiratory and gastrointestinal physiology: From molecular mechanisms to therapeutic targets.Frontiers in physiology · 2024Review
- Roles of airway and intestinal epithelia in responding to pathogens and maintaining tissue homeostasis.Frontiers in cellular and infection microbiology · 2024Review
- TRPV1 controls innate immunity during Citrobacter rodentium enteric infection.PLoS pathogens · 2023Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTransient Receptor Potential Ankyrin 1 (TRPA1) is a cation channel that mediates pain, itch, cough, and neurogenic inflammation in response to pungent compounds such as acrolein in cigarette smoke. TRPA1 is also activated by endogenous factors and promotes inflammation in asthma models. We have recently shown that TRPA1 is upregulated by inflammatory cytokines in A549 human lung epithelial cells. Here, we explored the effects of Th1 and Th2-type inflammation on TRPA1. METHODS AND
resultsTRPA1 expression and function was studied in A549 human lung epithelial cells. To induce inflammation, the cells were exposed to a combination of cytokines TNF-α and IL-1β; and to model Th1 or Th2-type responses, IFN-γ or IL-4/IL-13 was added, respectively. TRPA1 expression (measured by RT-PCR and Western blot) and function (assessed by Fluo-3AM intracellular calcium measurement) was enhanced under the influence of TNF-α + IL-1β. IFN-γ further enhanced TRPA1 expression and function, whereas IL-4 and IL-13 suppressed them. The effects of IFN-γ and IL-4 on TRPA1 expression were reversed by the Janus kinase (JAK) inhibitors baricitinib and tofacitinib, and those of IL-4 also by the STAT6 inhibitor AS1517499. The glucocorticoid dexamethasone downregulated TRPA1 expression, whereas the PDE4 inhibitor rolipram had no effect. Under all conditions, TRPA1 blockade was found to reduce the production of LCN2 and CXCL6.
conclusionsTRPA1 expression and function in lung epithelial cells was upregulated under inflammatory conditions. IFN-γ further increased TRPA1 expression while IL-4 and IL-13 suppressed that in a JAK-STAT6 dependent manner which is novel. TRPA1 also modulated the expression of genes relevant to innate immunity and lung disease. We propose that the paradigm of Th1 and Th2 inflammation is a major determinant of TRPA1 expression and function, which should be considered when targeting TRPA1 for pharmacotherapy in inflammatory (lung) disease.
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