Sanaki Takao, Kasai-Yamamoto Erika, Yoshioka Takeshi, Sakai Shota, Yuyama Kohei, Fujiwara Takuji, Numata Yoshito, Igarashi Yasuyuki
Shionogi Innovation Center for Drug Discovery, Shionogi & Co., Ltd.
Shionogi Pharmaceutical Research Center, Shionogi & Co., Ltd.
J Oleo Sci. 2017 Jun 1;66(6):591-599. doi: 10.5650/jos.ess16227. Epub 2017 May 17.
Arachidonic acid (AA) plays a pivotal role in the development of edema via its oxidized metabolites derived from cyclooxygenase (COX) and lipoxygenase (LOX), and is recently recognized as an activator of TRPV3. However, it is not clear whether AA plays some TRPV3-mediated pathological roles in the development of edema. Pharmacological and histological studies using ICR and ICR mice indicated that higher ear edema responses to topical application of AA were observed in ICR mice compared with ICR mice. However, there was no difference in the ear edema response to 12-O-tetradecanoylphorbol 13-acetate, skin histology, and skin barrier function between these mouse strains. Furthermore, oxidized fatty acids from the lesional site were analyzed to elucidate the TRPV3-mediated pathological roles of AA, and the results revealed that there were no differences in the level of COX or LOX metabolites derived from AA between both mouse strains. We concluded that AA plays a role in the development of TRPV3-mediated ear edema and that this result may contribute to better understanding of the pathophysiological mechanisms involved in the development of a certain type of edema.
花生四烯酸(AA)通过其由环氧化酶(COX)和脂氧合酶(LOX)产生的氧化代谢产物在水肿形成过程中起关键作用,并且最近被认为是瞬时受体电位香草酸亚型3(TRPV3)的激活剂。然而,尚不清楚AA在水肿形成过程中是否发挥某些由TRPV3介导的病理作用。使用ICR小鼠和ICR小鼠进行的药理学和组织学研究表明,与ICR小鼠相比,ICR小鼠对局部应用AA表现出更高的耳部水肿反应。然而,这些小鼠品系之间对12 - O - 十四酰佛波醇13 - 乙酸酯的耳部水肿反应、皮肤组织学和皮肤屏障功能并无差异。此外,分析了病变部位的氧化脂肪酸以阐明AA由TRPV3介导的病理作用,结果显示两种小鼠品系之间源自AA的COX或LOX代谢产物水平并无差异。我们得出结论,AA在TRPV3介导的耳部水肿形成中起作用,并且这一结果可能有助于更好地理解特定类型水肿形成所涉及的病理生理机制。