Immunostimulative Activity of Low Molecular Weight Chitosans in RAW264.7 Macrophages.

Ning Wu,You-Le Qu,Xing-Wei Xiang,Yang Gao,Zheng-Shun Wen,Yan-Na Huang

doi:10.3390/md13106210

Abstract

Chitosan and its derivatives such as low molecular weight chitosans (LMWCs) have been reported to exert many biological activities, such as antioxidant and antitumor effects. However, complex and molecular weight dependent effects of chitosan remain controversial and the mechanisms that mediate these complex effects are still poorly defined. This study was carried out to investigate the immunostimulative effect of different molecular weight chitosan in RAW264.7 macrophages. Our data suggested that two LMWCs (molecular weight of 3 kDa and 50 kDa) both possessed immunostimulative activity, which was dependent on dose and, at the higher doses, also on the molecular weight. LMWCs could significantly enhance the the pinocytic activity, and induce the production of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interferon-γ (IFN-γ), nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in a molecular weight and concentration-dependent manner. LMWCs were further showed to promote the expression of the genes including iNOS, TNF-α. Taken together, our findings suggested that LMWCs elicited significantly immunomodulatory response through up-regulating mRNA expression of proinflammatory cytokines and activated RAW264.7 macrophage in a molecular weight- and concentration-dependent manner.

Highlights

Low immune function of an organism may result in the generation and development of a tumor, but may be one of the most important factors that prevent the tumor patient’s recovery.Immunomodulation through natural or synthetic substances may be considered an alternative for the prevention and cure of diseases [1]
low molecular weight chitosans (LMWCs), which are more effectively absorbed in the body than high molecular weight chitosan, suitable narrow molecular weight distribution and non-toxicity, could be applied most promisingly to pharmaceutical materials
3 kDa chitosan significantly promoted the production of tumor necrosis factor α (TNF-α), IFN-γ and interleukin 6 (IL-6) from RAW264.7 cells, 3 kDa chitosan up-regulated the mRNA expression levels of TNF-α. All these results suggested that 3 kDa chitosan would simultaneously induced T helper cell 1 (Th1)- and T helper cell 2 (Th2)-type response; 50 kDa chitosan promoted the production of TNF-α, which was consistent with a Th1 response elicited when macrophages phagocytose microparticles of chitin [28]

Summary

Introduction

Low immune function of an organism may result in the generation and development of a tumor, but may be one of the most important factors that prevent the tumor patient’s recovery.Immunomodulation through natural or synthetic substances may be considered an alternative for the prevention and cure of diseases [1]. Low immune function of an organism may result in the generation and development of a tumor, but may be one of the most important factors that prevent the tumor patient’s recovery. Macrophages play a significant role in the host defense mechanism. When activated, they activate phagocytic activity, produce and release reactive oxygen species (ROS). Macrophages can induce expression of accessory and costimulatory molecules that promote sustained stimulatory interactions with T cells and the generation of adaptive immunity. The basic mechanisms of the immunostimulatory, anti-tumor, bactericidal and other therapeutic effects of polysaccharides are thought to occur via activation of immune cells resulting in the induction of immune response. Macrophages were thought to be the important target cells of some antitumor and immunomodulatory drug [5]

Results

Discussion

Conclusion