Polysaccharide from wheat bran induces cytokine expression via the toll-like receptor 4-mediated p38 MAPK signaling pathway and prevents cyclophosphamide-induced immunosuppression in mice

摘要

ABSTRACT Wheat bran-derived polysaccharides have attracted particular attention due to their immunomodulatory effects. However, the molecular mechanisms underlying their functions are poorly understood. The current study was designed to examine the effect of wheat bran polysaccharide (WBP) on RAW 264.7 cells and the underlying signaling pathways, which have not been explored. In addition, we also investigated the immuno-enhancement effects of WBP on cyclophosphamide (CTX)-induced immunosuppression in mice. WBP significantly increased the concentrations of intracellular nitric oxide (NO) and cytokines such as prostaglandin E_(2)(PGE_(2)) and tumor necrosis factor-α (TNF-α) in RAW 264.7 cells. The result of RT-PCR analysis indicated that WBP also enhanced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α expression. Further analyses demonstrated that WBP rapidly activated phosphorylated p38 mitogen-activated protein kinase (MAPK) and the transcriptional activities of activator protein-1 (AP-1) and nuclear factor (NF)-κB via toll-like receptor 4 (TLR4). Furthermore, in vivo experiments revealed that WBP increased the spleen and thymus indices significantly, and markedly promoted the production of the serum cytokines IL-2 and IFN-γ in CTX-induced immunosuppressed mice. Taken together, these results suggest that WBP can improve immunity by enhancing immune function, and could be explored as a potential immunomodulatory agent in functional food.