Wu Ning, Wen Zheng-Shun, Xiang Xing-Wei, Huang Yan-Na, Gao Yang, Qu You-Le
Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, Food and Pharmacy College, Zhejiang Ocean University, Zhoushan 316000, China.
Zhejiang Marine Development Research Institute, Zhoushan 316000, China.
Mar Drugs. 2015 Sep 30;13(10):6210-25. doi: 10.3390/md13106210.
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.
壳聚糖及其衍生物，如低分子量壳聚糖（LMWCs），已被报道具有多种生物活性，如抗氧化和抗肿瘤作用。然而，壳聚糖复杂且依赖分子量的效应仍存在争议，介导这些复杂效应的机制也仍不清楚。本研究旨在探讨不同分子量壳聚糖对RAW264.7巨噬细胞的免疫刺激作用。我们的数据表明，两种低分子量壳聚糖（分子量分别为3 kDa和50 kDa）均具有免疫刺激活性，其活性取决于剂量，在较高剂量时还取决于分子量。低分子量壳聚糖能以分子量和浓度依赖的方式显著增强胞饮活性，并诱导肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、干扰素-γ（IFN-γ）、一氧化氮（NO）和诱导型一氧化氮合酶（iNOS）的产生。低分子量壳聚糖还进一步显示能促进包括iNOS、TNF-α等基因的表达。综上所述，我们的研究结果表明，低分子量壳聚糖通过上调促炎细胞因子的mRNA表达，以分子量和浓度依赖的方式显著引发免疫调节反应并激活RAW264.7巨噬细胞。
