Abstract
Diphlorethohydroxycarmalol (DPHC) is a phlorotannin compound isolated from Ishige okamuarae, a brown alga. This study was conducted to investigate the anti-inflammatory effect and action mechanism of DPHC in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We found that DPHC strongly reduces the production of interleukin 6 (IL-6), but not that of tumor necrosis factor-alpha (TNF-α) induced by LPS. DPHC (12.5 and 100 μM) suppressed the phosphorylation and the nuclear translocation of NF-kappaB (NF-κB), a central signaling molecule in the inflammation process induced by LPS. The suppressor of cytokine signaling 1 (SOCS1) is a negative feedback regulator of Janus kinase (Jak)-signal transducer and activator of transcription (STAT) signaling. In this study, DPHC inhibited STAT5 expression and upregulated that of SOCS1 at a concentration of 100 μM. Furthermore, N-tosyl-l-phenylalanine chloromethyl ketone (TPCK) (a specific NF-κB inhibitor) and JI (a specific Jak2 inhibitor) reduced the production of IL-6, but not that of tumor necrosis factor-alpha (TNF-α) in LPS-stimulated RAW 264.7 macrophages. These findings demonstrate that DPHC inhibits IL-6 production via the downregulation of NF-κB and Jak2-STAT5 pathway and upregulation of SOCS1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Cutaneous
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
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Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
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Dermatitis, Atopic / immunology
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Dermatitis, Atopic / pathology
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Dermatitis, Atopic / prevention & control
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Dose-Response Relationship, Drug
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Female
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Gene Expression Regulation / drug effects
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Heterocyclic Compounds, 3-Ring / administration & dosage
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Heterocyclic Compounds, 3-Ring / isolation & purification
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Heterocyclic Compounds, 3-Ring / pharmacology*
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Heterocyclic Compounds, 3-Ring / therapeutic use
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Interleukin-6 / antagonists & inhibitors*
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Interleukin-6 / metabolism
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Lipopolysaccharides / antagonists & inhibitors
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Lipopolysaccharides / toxicity
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Macrophages / drug effects*
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Macrophages / immunology
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Macrophages / metabolism
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Mice
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Mice, Inbred BALB C
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / metabolism
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Pacific Ocean
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Phaeophyceae / chemistry
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Phaeophyceae / growth & development
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RAW 264.7 Cells
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Republic of Korea
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STAT5 Transcription Factor / antagonists & inhibitors*
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STAT5 Transcription Factor / genetics
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STAT5 Transcription Factor / metabolism
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Skin / drug effects
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Skin / immunology
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Skin / pathology
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Specific Pathogen-Free Organisms
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Suppressor of Cytokine Signaling 1 Protein
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Suppressor of Cytokine Signaling Proteins / agonists*
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Suppressor of Cytokine Signaling Proteins / antagonists & inhibitors
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Suppressor of Cytokine Signaling Proteins / genetics
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Suppressor of Cytokine Signaling Proteins / metabolism
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Heterocyclic Compounds, 3-Ring
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Interleukin-6
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Lipopolysaccharides
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NF-kappa B
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STAT5 Transcription Factor
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Socs1 protein, mouse
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Suppressor of Cytokine Signaling 1 Protein
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Suppressor of Cytokine Signaling Proteins
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diphlorethohydroxycarmalol
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interleukin-6, mouse
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lipopolysaccharide, Escherichia coli O111 B4