RESUMEN
Neobavaisoflavone (Neo), is the active constituent of the herb Psoralea corylifolial, used in the traditional Chinese medicine, and has anti-inflammatory activity, but whether Neo could regulate colitis remains unclear. T helper 9 (TH9) cells, a subset of CD4+ T helper cells characterized by secretion of IL-9, have been reported to be involved in the pathogenesis of many autoimmune and inflammatory diseases, but whether Neo could control TH9 cell differentiation also remains unclear. Here, we found that Neo could decrease IL-9 production of CD4+ T cells by targeting PU.1 in vitro. Importantly, Neo had therapeutic effects on DSS-induced colitis. Furthermore, we identified TH9 cells as the direct target of Neo for attenuating bowel inflammation. Therefore, Neo could serve as a lead for developing new therapeutics against inflammatory bowel disease.
Asunto(s)
Antiinflamatorios/uso terapéutico , Diferenciación Celular/efectos de los fármacos , Colitis/tratamiento farmacológico , Isoflavonas/uso terapéutico , Linfocitos T Colaboradores-Inductores/efectos de los fármacos , Animales , Antiinflamatorios/farmacología , Colitis/inmunología , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Immunoblotting , Isoflavonas/farmacología , Ratones , Ratones Endogámicos C57BL , Microscopía Confocal , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
The Chinese herbal medicine oridonin has potent anti-inflammatory and antitumor activities. In addition, oridonin treatment effectively suppresses breast cancer growth. However, the underlying mechanisms are poorly defined. Here, we reported that oridonin decreased Treg differentiation in vitro and in vivo. Oridonin inhibition of Treg differentiation was dependent on decreasing TGF-ß receptor expression. Oridonin attenuated Tregs' immunosuppressive ability; thus, oridonin did not inhibit CD8+ T cell proliferation very well in vitro. Oridonin greatly delayed the progression of 4T1 tumors in vivo. In addition, oridonin combined with anti-PD-1 activated a robust antitumor immune response and suppressed 4T1 tumor growth. Therefore, our results indicate that oridonin inhibits TNBC growth by modulating Treg differentiation, which provides new directions for the clinical treatment of TNBC.