Abstract
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 (PGE2) 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-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). GAC inactivated nuclear factor-κB (NF-κB) via inhibiting the phosphorylation and degradation of the NF-κB inhibitor, IκB. 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-κB and AP-1) through MAPK signaling pathways.
Keywords:
AP-1; MAPK; NF-κB; RAW macrophage; chitosan; inflammation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / pharmacology*
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Cell Line
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Chitosan / analogs & derivatives*
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Chitosan / chemistry
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Chitosan / pharmacology*
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Cyclooxygenase 2 / biosynthesis
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Dinoprostone / biosynthesis
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Enzyme Activation
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Gallic Acid / chemistry
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Gallic Acid / pharmacology*
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I-kappa B Kinase / metabolism
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Inflammation / drug therapy
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Interleukin-1beta / biosynthesis
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Interleukin-1beta / genetics
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Interleukin-6 / biosynthesis
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Interleukin-6 / genetics
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JNK Mitogen-Activated Protein Kinases / metabolism
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Lipopolysaccharides
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MAP Kinase Signaling System / drug effects*
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Macrophages / immunology
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Macrophages / metabolism
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Mice
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Nitric Oxide / biosynthesis
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Nitric Oxide Synthase Type II / biosynthesis
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Phosphorylation
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Transcription Factor AP-1 / metabolism*
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Transcription Factor RelA / genetics
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Transcription Factor RelA / metabolism
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Transcription Factor RelA / urine*
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / genetics
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Anti-Inflammatory Agents
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IL1B protein, mouse
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Interleukin-1beta
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Interleukin-6
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Lipopolysaccharides
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Rela protein, mouse
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Transcription Factor AP-1
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Transcription Factor RelA
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Tumor Necrosis Factor-alpha
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gallic acid-g-chitosan
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Nitric Oxide
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Gallic Acid
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Chitosan
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Nitric Oxide Synthase Type II
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Ptgs2 protein, mouse
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Cyclooxygenase 2
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I-kappa B Kinase
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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Dinoprostone