Diphlorethohydroxycarmalol inhibits interleukin-6 production by regulating NF-κB, STAT5 and SOCS1 in lipopolysaccharide-stimulated RAW264.7 cells

• Published in: Marine drugs Vol. 13; no. 4; pp. 2141 - 2157
• Main Authors: Kang, Na-Jin, Han, Sang-Chul, Kang, Gyeoung-Jin, Koo, Dong-Hwan, Koh, Young-Sang, Hyun, Jin-Won, Lee, Nam-Ho, Ko, Mi-Hee, Kang, Hee-Kyoung, Yoo, Eun-Sook
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 13.04.2015; MDPI AG
• Subjects: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - isolation & purification; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Dermatitis, Atopic - immunology; Dermatitis, Atopic - pathology; Dermatitis, Atopic - prevention & control; diphlorethohydroxycarmalol (DPHC); Dose-Response Relationship, Drug; Female; Gene Expression Regulation - drug effects; Heterocyclic Compounds, 3-Ring - administration & dosage; Heterocyclic Compounds, 3-Ring - isolation & purification; Heterocyclic Compounds, 3-Ring - pharmacology; Heterocyclic Compounds, 3-Ring - therapeutic use; IL-6; inflammation; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - metabolism; Jak-STAT; Lipopolysaccharides - antagonists & inhibitors; Lipopolysaccharides - toxicity; LPS; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Marine; Mice; Mice, Inbred BALB C; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-κB; Pacific Ocean; Phaeophyceae - chemistry; Phaeophyceae - growth & development; RAW 264.7 Cells; Republic of Korea; Skin - drug effects; Skin - immunology; Skin - pathology; SOCS; Specific Pathogen-Free Organisms; STAT5 Transcription Factor - antagonists & inhibitors; STAT5 Transcription Factor - genetics; STAT5 Transcription Factor - metabolism; Suppressor of Cytokine Signaling 1 Protein; Suppressor of Cytokine Signaling Proteins - agonists; Suppressor of Cytokine Signaling Proteins - antagonists & inhibitors; Suppressor of Cytokine Signaling Proteins - genetics; Suppressor of Cytokine Signaling Proteins - metabolism
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md13042141

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.