15‐hydroxy eicosadienoic acid is an exacerbating factor for nasal congestion in mice
15‐hydroxy eicosadienoic acid is an exacerbating factor for nasal congestion in mice
复制标题
15-羟基二十碳二烯酸是小鼠鼻塞的加剧因素
DOI：
10.1096/fj.202101305r
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Murata Takahisa
中科院分区：
文献类型：
--
作者：
Miyata Kana;Horikami Daiki;Tachibana Yuri;Yamamoto Teruko;Nakamura Tatsuro;Kobayashi Koji;Murata Takahisa
变应性鼻炎(AR)是全球最常见的变态反应性炎症性疾病之一。在变应性鼻炎中，鼻黏膜血流量和血管通透性增加会导致鼻漏和鼻塞。我们研究了一种11z，14Z-二十碳二烯酸衍生的代谢物15-羟基-11z，13Z-二十碳二烯酸(15-Hede)在AR血管功能改变和鼻塞中的作用。反复鼻腔注射卵清蛋白(OVA)会引起小鼠的AR症状，如打喷嚏和鼻塞。OVA治疗可增加鼻腔灌洗液中15-Hede的水平，经10次OVA治疗后，15-Hede水平约为0.6 ng/ml。在测量血管收缩时，0.1-3μM 15-Hede处理没有引起小鼠主动脉收缩，但它扩张了因血栓素受体刺激而预收缩的主动脉。电压门控性K+(KV)通道阻断剂4-氨基吡啶可显著抑制15-Hede的血管松弛作用。活体成像显示，给予1μg 15-Hede使血管扩张，Mile‘s试验表明，该给药也导致染料渗漏，表明小鼠耳朵血管通透性高。CT扫描和形态学研究显示，给予3μg 15-Hede后，小鼠的鼻腔通道变窄，鼻黏膜增厚。最后，我们证实，用3μg 15-Hede治疗小鼠会引起鼻炎症状，如腹部呼吸，并减少呼吸频率，这表明鼻塞。15-Hede通过激活KV通道和增加血管通透性而引起血管扩张，这可能导致鼻塞。此外，15-Hede可能是一种新的脂质介质，可加重AR患者的鼻塞。
Allergic rhinitis (AR) is one of the most common allergic inflammatory diseases worldwide. In AR, increased blood flow and vascular permeability in nasal mucosa cause rhinorrhea and nasal congestion. We investigated the role of an 11Z,14Z‐eicosadienoic acid‐derived metabolite, 15‐hydroxy‐11Z,13Z‐eicosadienoic acid (15‐HEDE), in functional changes in vasculature and nasal congestion in AR. Repeated intranasal administration of Ovalbumin (OVA) caused AR symptoms, such as sneezing and nasal congestion, in mice. OVA administration increased the level of 15‐HEDE in nasal lavage fluid, which reached approximately 0.6 ng/ml after ten OVA treatments. Upon measuring vascular contraction, treatment with 0.1–3 μM 15‐HEDE did not cause contraction in mouse aortae, while it dilated aortae that were pre‐contracted by thromboxane receptor stimulation. Pretreatment with the voltage‐gated K+(KV) channel inhibitor 4‐aminopyridine significantly inhibited the 15‐HEDE‐induced vascular relaxation. Intravital imaging showed that administration of 1 μg 15‐HEDE dilated blood vessels, and Mile's assay demonstrated that this administration also caused dye leakage, indicating vascular hyperpermeability in mouse ears. Computed tomography scanning and morphological study revealed that administration of 3 μg 15‐HEDE narrowed nasal passages and thickened nasal mucosa in mice. Finally, we confirmed that treating mice with 3 μg 15‐HEDE caused rhinitis symptoms, such as abdominal breathing, and reduced respiratory frequency, suggesting nasal congestion. 15‐HEDE caused vasodilation by activating KVchannels and increased vascular permeability, which may lead to nasal congestion. Furthermore, 15‐HEDE might be a new lipid mediator that exacerbates nasal congestion in AR.