Structure driven immunomodulatory properties of xylo-/arabinoxylo-oligosaccharides and arabinoxylans in RAW264.7 macrophages
Graphical abstract
Introduction
Arabinoxylan (AX) is a major polymer of the cell wall of many cereal grains (Saulnier, Sado, Branlard, Charmet, & Guillon, 2007). The general structure of AX can be described as a polysaccharide of β-(1,4)-linked xylose residues, which are substituted with arabinose residues on the C(O)−2 and/or C(O)−3 positions of xylose (Dornez, Gebruers, Delcour, & Courtin, 2009). Thus, hydrolysis products of AX can give rise to an array of oligosaccharides that are varying in degree of polymerization (DP) and degree of arabinose substitution (DS). Arabinoxylans are considered as dietary fibers, and owing to these properties, can contribute to many of the health benefits associated with dietary fibers. They are also suggested to contain possible immunomodulatory properties as demonstrated by many researchers (Gollapudi and Ghoneum, 2008, Pérez-Martínez et al., 2015, Zheng et al., 2012).
MGN-3/Biobran is a enzymatically modified AX, derived from rice bran (Ghoneum & Abedi, 2004). Using three types of macrophages, the human macrophage U937 cell line, the murine macrophage RAW264.7 cell line, and murine peritoneal macrophages (P-M phi), Ghoneum and Matsuura (2004) indicated that MGN-3 increased the attachment and phagocytosis of yeast by these macrophages in a dose dependent manner. They also observed enhanced spreading abilities and increased NO production in macrophages upon MGN-3 treatment (Ghoneum & Matsuura, 2004). Furthermore, the production of TNF-α and IL-6 was significantly increased in a dose dependent manner (1, 10,100 µg/mL) in these macrophages upon treatment with MGN-3.
AXs have been shown to impact the production of different cytokines. Ogawa et al. showed that oral administration of corn husk AXs to healthy mice resulted in significant increases in interleukin (IL)−2 and interferon (IFN)-γ production (Ogawa, Takeuchi, & Nakamura, 2005).
While the current literature strongly suggests that AX possesses immunological properties, little is known about the association between the structural properties of AXs and their immunological properties. Zhou et al. demonstrated that the immunological properties of AXs are dependent on their molecular weight, chemical composition and substitution of arabinose (Zhou et al., 2010). According to a research by Monobe et al. wheat bran derived AX was shown to contain higher immunostimulating activity than AX derived from corn husk or rice bran (Monobe, Maeda-Yamamoto, Matsuoka, Kaneko, & Hiramoto, 2008). Wheat flour derived enzymatic modified arabinoxylan (AX) which contained higher degree of branching was shown to have higher NO2− stimulatory effect and higher IL-8 production compared to wheat flour AX which contained lower degree of branching (Li, Zhang, & Smith, 2015). We thus aimed to further evaluate the structure-function relationship of AX as immunomodulators, in terms of DP, DS and size of AX by employing an array of xylo-oligosaccharides (XOS), and arabinoxylo-oligosaccharides (AXOS) with different degree of polymerization and different degree of arabinose substitution.
Section snippets
Materials
Xylo-oligosaccharides (XOS), arabinoxylo- oligosaccharides (AXOS) and arabinoxylan polysaccharides were purchased from Megazyme (Bray, Ireland) who produce oligosaccharides of high purity level (90–95% purity) which were produced from plant sources and were chromatographically purified. Thus, it is unlikely that these oligosaccharides contained Lipopolysaccharides (LPS) contamination. The murine macrophage RAW264.7 cell line were obtained from the American Type Culture Collection (ATCC)
Effect of XOS, AXOS and AX polysaccharides on NO production
Upon stimulation by microbes or cytokines, macrophages are capable of producing NO from L-arginine. NO functions as a mediator of immune functions (Abbas and Lichtman, 2011, Moncada et al., 1991). Although NO is a vital component of a healthy immune system, increased NO production can result in adverse health outcomes (Moncada, Palmer, & Higgs, 1991). Thus, careful regulation of inflammatory molecules such as NO might be useful in the treatment of chronic inflammation derived diseases such as
Conclusion
We have used an array of oligosaccharides and polysaccharides in an effort to determine the structure-function relationship of these substrates as immunomodulators. To determine potential immunomodulatory effects, we stimulated human macrophages RAW264.7 in culture and determine the levels of NO and the pro-inflammatory cytokine TNF-α. We observed that overall the XOS tested did not exert significant immunomodulatory properties, only a modest effect was observed with X3, which resulted in a
Acknowledgements
We acknowledge the College of Health Profession at North Dakota State University for their collaboration for this research and North Dakota Wheat Commission and for funding this research.
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