1. Pentanoic acid induces thymic stromal lymphopoietin production through G q/11 and Rho-associated protein kinase signaling pathway in keratinocytes.
- Author
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Mizuno N, Abe K, Morishita Y, Yamashita S, Segawa R, Dong J, Moriya T, Hiratsuka M, and Hirasawa N
- Subjects
- Amides pharmacology, Animals, Cells, Cultured, GTP-Binding Protein alpha Subunits, Gq-G11 genetics, Humans, Keratinocytes physiology, Mice, Mice, Inbred BALB C, Pentanoic Acids immunology, Peptides, Cyclic pharmacology, Pyridines pharmacology, RNA, Small Interfering genetics, Signal Transduction, Skin pathology, rho-Associated Kinases metabolism, Thymic Stromal Lymphopoietin, Cytokines metabolism, GTP-Binding Protein alpha Subunits, Gq-G11 metabolism, Hypersensitivity immunology, Keratinocytes drug effects, Pentanoic Acids metabolism, Skin immunology
- Abstract
Thymic stromal lymphopoietin (TSLP) plays an important role in allergic skin inflammation. Short-chain fatty acids (SCFAs), including pentanoic acid, are products of bacterial metabolism and are associated with allergic skin disorders. However, whether SCFAs induce TSLP production is still unclear. In this study, we evaluated the effect of SCFAs on TSLP production and found that pentanoic acid was the most efficacious of the tested SCFAs. The G
q/11 inhibitor YM-254890 and the Rho-associated protein kinase (ROCK) inhibitor Y-27632 inhibited pentanoic acid-induced TSLP production, as did transfection with Gq/11 siRNA. These results suggested that pentanoic acid-induced TSLP production was mediated by Gq/11 and ROCK, providing insights into a novel TSLP production pathway in keratinocytes. The novel mechanism of TSLP production is expected to support the development of TSLP-regulating approaches in allergic skin disorders., (Copyright © 2017 Elsevier B.V. All rights reserved.)- Published
- 2017
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