Abstract
ABSTRACTWheat 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.
Highlights
Immunostimulation, regarded as one of the body’s important defenses, plays a significant role in the host defense mechanism against the invasion of pathogens and antigens. [1] Macrophages derived from blood monocytes can initiate an innate immune response by recognizing infectious agents, and thereby inhibit the growth of a wide variety of tumor cells and invasion of microorganisms.[2,3]Polysaccharides, as a primary class of biomacromolecules, are composed of monosaccharides and are distributed widely among animals, plants, algae, and fungi.[4]
Macrophages can kill pathogens directly by phagocytosis and indirectly through secreting inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6.[9,10] Polysaccharide-mediated immune cell stimulation can occur via binding to pattern recognition receptors (PRRs) on the surface of macrophages such as toll-like receptors (TLRs), Dectin-1, and complement receptor type 3 (CR3), and trigger a series of signal transduction pathways including phosphoinositide-3-kinase (PI3K)/Akt, mitogen-activated protein kinases (MAPKs), as well as transcription factors such as nuclear factor (NF)κB and activator protein (AP)-1.[11,12]
It is well known that protein by amide bond and ferulic acid are bonded with polysaccharide by a covalent ester bond to form the water-insoluble polymer
Summary
Polysaccharides, as a primary class of biomacromolecules, are composed of monosaccharides and are distributed widely among animals, plants, algae, and fungi.[4] In recent years, numerous polysaccharides isolated from natural resources have been demonstrated to possess a broad spectrum of therapeutic properties such as antioxidant, anti-cancer, and immune-modulating activities, and have been used widely in the food and pharmaceutical industries.[5,6,7] Several plant polysaccharides have been regarded as important immunostimulant candidates due to their ability to enhance the activation of macrophages with no significant side effects and low toxicity.[8] When activated, macrophages can kill pathogens directly by phagocytosis and indirectly through secreting inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6.[9,10] Polysaccharide-mediated immune cell stimulation can occur via binding to pattern recognition receptors (PRRs) on the surface of macrophages such as toll-like receptors (TLRs), Dectin-1, and complement receptor type 3 (CR3), and trigger a series of signal transduction pathways including phosphoinositide-3-kinase (PI3K)/Akt, mitogen-activated protein kinases (MAPKs), as well as transcription factors such as nuclear factor (NF)κB and activator protein (AP)-1.[11,12].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
