Mizuno Natsumi, Abe Koudai, Morishita Yukari, Yamashita Saori, Segawa Ryosuke, Dong Jiangxu, Moriya Takahiro, Hiratsuka Masahiro, Hirasawa Noriyasu
Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan.
Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan.
Int Immunopharmacol. 2017 Sep;50:216-223. doi: 10.1016/j.intimp.2017.06.024. Epub 2017 Jul 3.
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 inhibitor YM-254890 and the Rho-associated protein kinase (ROCK) inhibitor Y-27632 inhibited pentanoic acid-induced TSLP production, as did transfection with G siRNA. These results suggested that pentanoic acid-induced TSLP production was mediated by G 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.
胸腺基质淋巴细胞生成素(TSLP)在过敏性皮肤炎症中起重要作用。包括戊酸在内的短链脂肪酸(SCFAs)是细菌代谢产物,与过敏性皮肤疾病有关。然而,SCFAs是否诱导TSLP产生仍不清楚。在本研究中,我们评估了SCFAs对TSLP产生的影响,发现戊酸是所测试的SCFAs中最有效的。G抑制剂YM-254890和Rho相关蛋白激酶(ROCK)抑制剂Y-27632抑制了戊酸诱导的TSLP产生,用G小干扰RNA转染也有同样效果。这些结果表明,戊酸诱导的TSLP产生是由G和ROCK介导的,这为角质形成细胞中一种新的TSLP产生途径提供了见解。TSLP产生的新机制有望为过敏性皮肤疾病中TSLP调节方法的开发提供支持。