Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Kyoto, Japan.
Laboratory of Pathophysiology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kodo Kyotanabe, Kyoto, 610-0395, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Aug;397(8):6061-6074. doi: 10.1007/s00210-024-02969-0. Epub 2024 Feb 23.
The prevalence of food allergy (FA) has increased worldwide but an effective therapeutic strategy has not been established. Transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive nonselective cation channel, is mainly expressed in the epithelium of various organs. The present study investigated the role of TRPV4 in the pathogenesis of an ovalbumin (OVA)-induced FA model in mice. Wild-type (WT) and TRPV4-deficient (TRPV4KO) mice were sensitized and challenged by OVA to establish FA model. Intestinal tissue samples were processed for biochemical, molecular, and image analyses. Intestinal permeability and antigen uptake assay were conducted using FITC-dextran and OVA-FITC, respectively. TRPV4 was expressed in the colonic epithelium in normal and OVA-treated WT mice. Repeated oral administration of OVA to mice induced systemic allergic symptoms, diarrhea, upregulation of T helper 2 cytokines, OVA-specific immunoglobulin, and FA-related inflammatory cells. These responses were significantly augmented in TRPV4KO mice compared with WT mice. After the induction of FA, the intestinal permeability was significantly increased in TRPV4KO mice compared with WT mice. The expressions of the tight junction protein occludin and adherence junction protein E-cadherin in the colon were significantly lower in TRPV4KO mice compared with WT mice under normal and FA conditions. In addition, the uptake of OVA by CD11c-positive cells was significantly increased in TRPV4KO mice compared with WT mice under FA conditions. These results suggest that epithelial TRPV4 protects against OVA-induced FA symptoms by suppressing the penetration of allergens by maintaining epithelial barrier functions.
食物过敏（FA）的患病率在全球范围内有所增加，但尚未建立有效的治疗策略。瞬时受体电位香草醛 4（TRPV4）是一种机械敏感的非选择性阳离子通道，主要表达在各种器官的上皮细胞中。本研究探讨了 TRPV4 在卵清蛋白（OVA）诱导的 FA 模型小鼠发病机制中的作用。野生型（WT）和 TRPV4 缺陷型（TRPV4KO）小鼠通过 OVA 致敏和攻毒建立 FA 模型。对肠组织样本进行生化、分子和图像分析。使用 FITC-葡聚糖和 OVA-FITC 分别进行肠通透性和抗原摄取测定。TRPV4 在正常和 OVA 处理的 WT 小鼠的结肠上皮中表达。反复口服 OVA 诱导小鼠产生全身性过敏症状、腹泻、辅助性 T 细胞 2 细胞因子、OVA 特异性免疫球蛋白和 FA 相关炎症细胞上调。与 WT 小鼠相比，TRPV4KO 小鼠的这些反应明显增强。在 FA 诱导后，TRPV4KO 小鼠的肠通透性明显高于 WT 小鼠。在正常和 FA 条件下，与 WT 小鼠相比，TRPV4KO 小鼠结肠中的紧密连接蛋白 occludin 和黏附连接蛋白 E-钙黏蛋白表达明显降低。此外，在 FA 条件下，CD11c 阳性细胞摄取 OVA 的量在 TRPV4KO 小鼠中明显高于 WT 小鼠。这些结果表明，上皮细胞 TRPV4 通过维持上皮屏障功能来抑制过敏原的穿透，从而防止 OVA 诱导的 FA 症状。
