Gallic Acid-g-Chitosan Modulates Inflammatory Responses in LPS-Stimulated RAW264.7 Cells Via NF-κB, AP-1, and MAPK Pathways
Gallic Acid-g-Chitosan Modulates Inflammatory Responses in LPS-Stimulated RAW264.7 Cells Via NF-κB, AP-1, and MAPK Pathways
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DOI：
10.1007/s10753-015-0258-2
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发表时间：
2016-02-01
期刊：
影响因子：
5.1
通讯作者：
Je, Jae-Young
中科院分区：
文献类型：
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作者：
Ahn, Chang-Bum;Jung, Won-Kyo;Je, Jae-Young
壳聚糖是一种天然存在的多糖，其具有抗氧化、抗微生物和抗癌等活性。壳聚糖接枝酚类化合物是提高壳聚糖生物活性的有效途径。我们研究了没食子酸接枝壳聚糖（GAC）在脂多糖（LPS）刺激的RAW 264.7巨噬细胞中的抗炎作用。GAC通过抑制LPS刺激的RAW 264.7巨噬细胞诱导型一氧化氮合酶（iNOS）和环氧合酶-2（考克斯-2）的表达，抑制NO和前列腺素E2（PGE（2））的产生。GAC还抑制促炎细胞因子如肿瘤坏死因子α（TNF-α）、白细胞介素-1 β（IL-1 β）和白细胞介素-6（IL-6）的产生和mRNA表达。GAC通过抑制核因子-κ B抑制剂I κ B的磷酸化和降解而灭活核因子-κ B（NF-κ B）。此外，GAC通过细胞外信号调节激酶（ERK 1/2）、p38 MAPK和c-Jun N-末端激酶/应激活化蛋白激酶（JNK）等促分裂原活化蛋白激酶（MAPK）的磷酸化抑制活化蛋白-1（AP-1）的活化。这些结果表明，GAC具有潜在的抗炎作用，通过下调转录因子（NF-κ B和AP-1）通过MAPK信号通路。
Chitosan is a naturally occurring polysaccharide, which has exhibited antioxidant, antimicrobial, and anti-cancer activities among others. Modification of chitosan by grafting phenolic compounds is a good strategy for improvement of bioactivities of chitosan. We investigated the anti-inflammatory action of gallic acid-grafted-chitosan (GAC) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. GAC inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE(2)) by inhibiting inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-stimulated RAW264.7 macrophages. GAC also suppressed the production and mRNA expression of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6). GAC inactivated nuclear factor-kappa B (NF-kappa B) via inhibiting the phosphorylation and degradation of the NF-kappa B inhibitor, I kappa B. In addition, GAC suppresses the activation of activator protein-1 (AP-1) through the phosphorylation of mitogen-activated protein kinase (MAPK) such as extracellular signal-regulated kinase (ERK1/2), p38 MAPK, and c-Jun N-terminal kinase/stress-activated protein kinase (JNK). These results suggest that GAC has the potential anti-inflammatory action by downregulating transcriptional factors (NF-kappa B and AP-1) through MAPK signaling pathways.