RESUMO
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-ß1 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-ß1 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.
Assuntos
Dermatite Atópica/tratamento farmacológico , Polissacarídeos/administração & dosagem , Polissacarídeos/uso terapêutico , Alga Marinha/química , Administração Tópica , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Dermatite Atópica/induzido quimicamente , Dinitroclorobenzeno/toxicidade , Esquema de Medicação , Masculino , Células B de Memória/efeitos dos fármacos , Células B de Memória/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/metabolismo , Polissacarídeos/química , Células RAW 264.7 , Linfócitos T Reguladores , Células Th2/efeitos dos fármacos , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Atopic dermatitis (AD) is a long-term allergic skin disorder that occurs most frequently in children. Currently, the common treatment of AD is corticosteroids; however, the drugs cause serious side effects. Therefore, there are many patients who seek complementary and alternative treatments such as healthy food. We report that fucoidan from Cladosiphon okamuranus (COP) exhibit exceptional immuno-modulatory effects significantly improving atopic dermatitis (AD) at both in vitro and in vivo levels: First, we performed the P815 cell degranulation assay, of which the results revealed that COP possesses anti-degranulation activity suggesting COP is very conducive to relieving allergic reactions of AD. Next, we performed the animal model examination, of which AD was significantly improved, suggesting COP can focally and globally modulate the immune systems of animals. The systemic improvements were manifested clearly by decreased epidermal hyperplasia, reduced infiltration of eosinophils, and decreased expression of AD-associated cytokines. Notably, COP reduced epidermal hyperplasia by downregulating the expression of IL-22. COP displayed therapeutic effects, which is comparable to corticosteroids but lack corticosteroid side effects, such as weight loss in our animal study. COP is multitudinous immunomodulatory abilities to serve as a healthy food supplement at the current stage, not least beneficial to atopic dermatitis.