Doctoral Degree Program in Marine Biotechnology, National Taiwan Ocean University, Keelung, Taiwan; Doctoral Degree Program in Marine Biotechnology, Academia Sinica, Taipei, Taiwan; Department of Food Science and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, Taiwan.
Department of Food Science and Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, Taiwan.
Int Immunopharmacol. 2021 Dec;101(Pt B):108362. doi: 10.1016/j.intimp.2021.108362. Epub 2021 Nov 18.
Atopic dermatitis (AD) is a T helper (Th) 2 cell-mediated allergic disease, which features increased number of immunocytes and level of Th2-associated cytokines. Fucoidan is well known a naturally occurring agent effectively ameliorating many AD symptoms. Though these alleviative effects are exhilarating, the mechanisms behind, however, are still rather limited. In this study, we report that fucoidan derived from Cladosiphon okamuranus (FT) inhibits nitric oxide (NO) production by exerting its anti-inflammatory ability. Topical application on animals show that FT promotes skin repair, reduces immunocyte proliferation, and decreases serum IgE level. In histological analysis, FT favorably reduces epidermal hyperplasia and eosinophilic infiltration. The pharmacodynamics mechanism of FT is determined by means of down-regulating AD-associated cytokines (IL-4, IL-5, IL-22, IL-33, and TSLP) and up-regulating TGF-β1 level. Moreover, FT can regulate systemic immunity by enhancing tolerogenic dendritic cells (Tol-DCs) to activate regulatory T cells (Treg) differentiation and to decrease the population of Th22 and memory B cells. Overall, topical application of FT is able to enhance Treg secreting TGF-β1 and to down-regulate Th2 cell-mediated immunity so that AD symptoms are significantly alleviated. Thereby, FT is an ideal drug candidate potentially replacing or complementing corticosteroids to be developed and used as a therapeutic agent to treat AD.
特应性皮炎（AD）是一种 Th2 细胞介导的过敏性疾病，其特征是免疫细胞数量增加和 Th2 相关细胞因子水平升高。褐藻糖胶是一种天然存在的有效改善许多 AD 症状的物质。尽管这些缓解作用令人振奋，但背后的机制仍然相当有限。在这项研究中，我们报告了来源于 Okamuranus 角叉菜（FT）的褐藻糖胶通过发挥其抗炎能力抑制一氧化氮（NO）的产生。动物的局部应用表明，FT 促进皮肤修复，减少免疫细胞增殖，并降低血清 IgE 水平。在组织学分析中，FT 有利于减少表皮增生和嗜酸性粒细胞浸润。FT 的药效学机制是通过下调 AD 相关细胞因子（IL-4、IL-5、IL-22、IL-33 和 TSLP）和上调 TGF-β1 水平来实现的。此外，FT 可以通过增强耐受性树突状细胞（Tol-DCs）来调节全身免疫，从而激活调节性 T 细胞（Treg）分化，并减少 Th22 和记忆 B 细胞的数量。总的来说，FT 的局部应用能够增强 Treg 分泌的 TGF-β1，并下调 Th2 细胞介导的免疫，从而显著缓解 AD 症状。因此，FT 是一种理想的药物候选物，可替代或补充皮质类固醇，作为治疗 AD 的治疗剂进行开发和使用。
