RESUMEN
In previous studies, Lycium barbarum polysaccharides (LBP), a traditional Chinese medicine, can promote immature dendritic cells (DCs) to mature. However, the molecular mechanisms by which LBP works are not yet elucidated. Here, we found that LBP can induce DCs maturation, which is mainly characterized by the upregulation of MHCII and costimulatory molecules (CD80, CD86), and increase the production of IL-6 and IL-4. Furthermore, we found that LBP could increase the mRNA and protein expression of TLR4, p38, Erk1/2, JNK, and Blimp1 signal molecules. More interestingly, after blocking by Toll-like receptor 4 inhibitor, Resatorvid (TAK 242), the mRNA and protein expression of TLR4, Erk1/2, and Blimp1 was significantly decreased while the expression of p38 and JNK has not changed. Then, we found that after blocking by p38 inhibitor (SB203580), Erk inhibitor (PD98059), and JNK inhibitor (SP603580) separately, Blimp1 protein expression was significantly reduced; after downregulating Blimp1 by Blimp1-siRNA, the production of IL-6 was reduced. In conclusion, our results indicate that LBP can induce maturation of DCs through the TLR4-Erk1/2-Blimp1 signal pathway instead of the JNK/p38-Blimp1 pathway. Our findings may provide a novel evidence for understanding the molecular mechanisms of LBP on activating murine DCs.
Asunto(s)
Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Medicamentos Herbarios Chinos/farmacología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Factor 1 de Unión al Dominio 1 de Regulación Positiva/metabolismo , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Animales , Biomarcadores , Línea Celular Tumoral , Citocinas/metabolismo , Regulación de la Expresión Génica , Inmunohistoquímica , Ratones , ARN Interferente Pequeño/genética , Receptor Toll-Like 4/genéticaRESUMEN
Lycium barbarum polysaccharides (LBP) have been shown to play a variety of immune-modulatory functions which include activation of T and B cells. Follicular helper T (Tfh) cells are now recognized as a subset of helper T cells which regulate the multiple stages of B cell maturation and function. In our current study, we found that LBP were able to activate CXCR5+PD-1+ Tfh cells and induce IL-21 secretion. At the same time LBP also promoted the formation of germinal centers (GC) and production of GL-7+B220+GC B cells. LBP as an adjuvant could increase generation of rAd5VP1-induced Tfh cells. Our results indicate that LBP might enhance T cell-dependent Ab responses by acting as an adjuvant for the generation of Tfh cells. Future vaccine designs might therefore be targeted to induce strong antigen-specific Tfh responses in order to boost its protective effects.