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

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 E2 (PGE2) 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.

In Vivo and In Vitro Study of Immunostimulation by Leuconostoc lactis-Produced Gluco-Oligosaccharides

“…myxogenes activate MAPK and NF-κB pathways and improve immunostimulatory activity in CY-induced imuunosuppressed mice [46]. Polysaccharides of Lonicera japonica , a typical Chinese herbal medicine, and wheat bran-derived polysaccharides markedly promote the serum cytokine levels [47,48], and polysaccharides derived from Stichopus japonicus (sea cucumber), up-regulate the expression of cytokines, such as IL-1β, IL-4, IL-6, IL-10, TNF-α, and IFN-γ, in the CY-induced mice [49]. As CCK-oligosaccharides have an immunostimulating activity, it can be used as an ingredient for functional foods to regulate immune responses.…”

Advances in Research on Immunoregulation of Macrophages by Plant Polysaccharides

“…Because activator protein 1 (AP-1) and MAPK are important downstream signaling molecules that mediate the activation of macrophages and the expression of inflammatory genes, T. Yeo Dae Yoon et al investigated the effect of PG on AP-1 and MAPK activity in the macrophage RAW264.7. The electrophoretic mobility shift assay (EMSA) results showed that PG significantly increases the DNA binding activity of AP-1, and further experiments demonstrated that PG activates three subgroups of MAPK (ERK1/2, SAPK/JNK, and p38 MAPK) (37, 66). When the induction effect of PG was detected after pretreatment of macrophages with specific inhibitors of these three kinases, PG did not show an activation effect, and the DNA binding activity of AP-1 was inhibited by the MAPK inhibitors.…”

[Retracted] Protective Effect of a Novel Polysaccharide from Lonicera japonica on Cardiomyocytes of Mice Injured by Hydrogen Peroxide

“…Some of them are components of the cell walls of plants, such as peptidoglycan and cellulose. Some are nutrients stored in plants and animals, such as glycogen and starch [14]. Scientific experiments show that many polysaccharides have biological activity, including immunomodulatory, antioxidation, antibacterial, and antitumor [15,16].…”