Abstract

Chitooligosaccharides (COS), the hydrolyzed products of chitin and chitosan, can be obtained by various methods. In this study, water-soluble COS were prepared from α- and β-chitosan by microwave-assisted degradation and their immunostimulatory effects were investigated in RAW 264.7 macrophages. The results indicated that α-COS were more active than β-COS in promoting the production of nitric oxide (NO) and cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6). Quantitative real-time reverse transcription polymerase chain reaction and Western blotting indicated that COS also enhanced the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α. Further analyses demonstrated that COS induced the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38, p85 and Akt, and the nuclear translocation of p65, indicating that they are able to activate the mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinases (PI3K)/Akt signaling pathways dependent on nuclear factor (NF)-κB activation. In conclusion, COS activate RAW 264.7 cells via the MAPK and PI3K/Akt signaling pathways and are potential novel immune potentiators.

Highlights

  • Immune responses are initiated by host defenses against invading pathogens via the innate and adaptive immune systems [1]

  • The spectrum of α-COS and β- chitooligosaccharide (β-COS) were similar to α- and β-chitosan with high molecular weight

  • The results indicated that the production of nitric oxide (NO) by macrophages was enhanced by increasing the COS concentration from 12.5 to 200 μg/mL (Figure 3A)

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Summary

Introduction

Immune responses are initiated by host defenses against invading pathogens via the innate and adaptive immune systems [1]. The immune responses of the elderly and patients with immunodeficiency diseases need to be enhanced. Immunoenhancing nutraceuticals and medicines have attracted a great deal of attention owing to their immunostimulatory activity. Macrophages and dendritic cells play pivotal roles in the immune system and activate immune responses via cytokine release, phagocytosis, and antigen presentation [2]. Macrophage activation is crucial for promoting immune activity [3]. Stimulated macrophages release various proinflammatory mediators and cytokines, including nitric oxide (NO), tumor necrosis factor-α (TNF-α), prostaglandin

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