Diphlorethohydroxycarmalol Inhibits Interleukin-6 Production by Regulating NF-κB, STAT5 and SOCS1 in Lipopolysaccharide-Stimulated RAW264.7 Cells

• DOI: 10.3390/md13042141
• Publication Date: 2015-04-14T07:11:46Z
• Authors: Na-Jin Kang; Sang-Chul Han; Gyeoung-Jin Kang; Dong-Hwan Koo; Young-Sang Koh; Jin-Won Hyun; Nam-Ho Lee; Mi-Hee Ko; Hee-Kyoung Kang; Eun-Sook Yoo
• Keywords: Lipopolysaccharides; 0301 basic medicine; LPS; Phaeophyceae; QH301-705.5; Administration, Cutaneous; NF-κB; Article; Dermatitis, Atopic; Mice; 03 medical and health sciences; Republic of Korea; STAT5 Transcription Factor; Animals; Biology (General); Skin; IL-6; Mice, Inbred BALB C; Pacific Ocean; Dose-Response Relationship, Drug; Interleukin-6; Macrophages; Anti-Inflammatory Agents, Non-Steroidal; NF-kappa B; Jak-STAT; SOCS; RAW 264.7 Cells; Gene Expression Regulation; inflammation; diphlorethohydroxycarmalol (DPHC); Female; Heterocyclic Compounds, 3-Ring

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.