Transient receptor potential ankyrin 1 promotes the expression of interferon-stimulated antiviral genes in human A549 lung epithelial cells.

Transient receptor potential ankyrin 1 (TRPA1) is an ion channel known for its chemosensory function in neurons, causing pain and neurogenic inflammation. TRPA1 is activated by many noxious compounds including some inflammatory mediators. We and others have shown that TRPA1 is also expressed in epithelial cells, but its function in the epithelial barrier remains unclear. Here, we discovered in RNA-seq studies that inhibition of TRPA1 reduced the expression of a large number of antiviral and inflammatory genes under the influence of the key antiviral cytokine interferon beta in human A549 lung epithelial cells. In the gene ontology analysis, the terms most strongly affected by TRPA1 antagonists included many associated with antiviral defense such as "defense response to virus" and "antiviral innate immune response." To validate the RNA-seq results, selected antiviral genes such as myxovirus resistance protein 1 were further studied and found to be upregulated by TRPA1 by using reverse transcription quantitative polymerase chain reaction and western blotting, pharmacological TRPA1 inhibitors, TRPA1-targeting small interfering RNA, and ex vivo lung tissue cultures from TRPA1-deficient mice. Mechanistically, TRPA1 inhibitors partially reduced interferon beta-induced Ca