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FASEB J ; 34(11): 14810-14819, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32964554

RESUMO

Dendritic cells (DCs) and T cells play important roles in immune regulation, and modulating their function is an approach for developing preventive or therapeutic strategies against immune disorders. Herein, the effect of pterostilbene (PSB) (3',5'-dimethoxy-resveratrol)-a resveratrol-related polyphenol found in blueberries-on immune regulation was evaluated. Using an in vitro co-culture system, PSB was found to exert the strongest inhibitory effect among all tested resveratrol derivatives on DC-mediated T cell proliferation; moreover, PSB treatment decreased the Th1 and Th17 populations and increased the regulatory T cell (Treg) population. Upon co-stimulation with anti-CD3 and anti-CD28 antibodies, PSB inhibited CD4+ T cell proliferation and differentiation into Th1 cells. Additionally, PSB acted on DCs to suppress the lipopolysaccharide-induced transactivation of genes encoding antigen presentation-related molecules and inflammatory cytokines by attenuating the DNA-binding ability of the transcription factor PU.1. Furthermore, PSB promoted DC-mediated Foxp3+ Treg differentiation, and PU.1 knockdown increased DC-induced Treg activity. Oral administration of PSB alleviated the symptoms of dextran sulfate sodium-induced colitis and decreased tumor necrosis factor-α expression in mice. Thus, PSB treatment ameliorates colonic inflammation.


Assuntos
Anti-Inflamatórios/farmacologia , Colite Ulcerativa/tratamento farmacológico , Células Dendríticas/imunologia , Estilbenos/farmacologia , Linfócitos T Reguladores/imunologia , Animais , Anti-Inflamatórios/uso terapêutico , Linhagem Celular , Proliferação de Células , Células Cultivadas , Colite Ulcerativa/imunologia , Colo/efeitos dos fármacos , Colo/imunologia , Citocinas/genética , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Fatores de Transcrição Forkhead/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas/metabolismo , Estilbenos/uso terapêutico , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/fisiologia , Células Th1/imunologia , Células Th1/fisiologia , Células Th17/imunologia , Células Th17/fisiologia , Transativadores/metabolismo
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