title: Diphlorethohydroxycarmalol inhibits interleukin-6 production by regulating NF-κB, STAT5 and SOCS1 in lipopolysaccharide-stimulated RAW264.7 cells.
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.
authors: Department of Biomedicine & Drug Development, Jeju National University, Jeju 690-756, Korea. najin0423@naver.com.
authors: Na-Jin
authors: NJ
authors: Kang
authors: Department of Medicine, Jeju National University School of Medicine, Jeju 690-756, Korea. hanschh@naver.com.
authors: Sang-Chul
authors: SC
authors: Han
authors: Department of Medicine, Jeju National University School of Medicine, Jeju 690-756, Korea. izar0824@nate.com.
authors: Gyeoung-Jin
authors: GJ
authors: Kang
authors: Department of Biomedicine & Drug Development, Jeju National University, Jeju 690-756, Korea. piofpe87@gmail.com.
authors: Dong-Hwan
authors: DH
authors: Koo
authors: Department of Biomedicine & Drug Development, Jeju National University, Jeju 690-756, Korea. yskoh7@jejunu.ac.kr.|Department of Medicine, Jeju National University School of Medicine, Jeju 690-756, Korea. yskoh7@jejunu.ac.kr.
authors: Young-Sang
authors: YS
authors: Koh
authors: Department of Biomedicine & Drug Development, Jeju National University, Jeju 690-756, Korea. jinwonh@jejunu.ac.kr.|Department of Medicine, Jeju National University School of Medicine, Jeju 690-756, Korea. jinwonh@jejunu.ac.kr.
authors: Jin-Won
authors: JW
authors: Hyun
authors: Department of Chemistry, School of Natural Science, Jeju National University, Jeju 690-756, Korea. namho@jejunu.ac.kr.
authors: Nam-Ho
authors: NH
authors: Lee
authors: Jeju Biodiversity Research Institute (JBRI), JejuTechnopark (JTP), Jeju 690-787, Korea. miheeko@jejutp.or.kr.
authors: Mi-Hee
authors: MH
authors: Ko
authors: Department of Biomedicine & Drug Development, Jeju National University, Jeju 690-756, Korea. pharmkhk@jejunu.ac.kr.|Department of Medicine, Jeju National University School of Medicine, Jeju 690-756, Korea. pharmkhk@jejunu.ac.kr.
authors: Hee-Kyoung
authors: HK
authors: Kang
authors: Department of Biomedicine & Drug Development, Jeju National University, Jeju 690-756, Korea. eunsyoo@jejunu.ac.kr.|Department of Medicine, Jeju National University School of Medicine, Jeju 690-756, Korea. eunsyoo@jejunu.ac.kr.
authors: Eun-Sook
authors: ES
authors: Yoo
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D003876:Dermatitis, Atopic / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010140:Pacific Ocean; D000459:Phaeophyceae / Q000737:chemistry / Q000254:growth & development; D000067996:RAW 264.7 Cells; D056910:Republic of Korea; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006575:Heterocyclic Compounds, 3-Ring; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D050799:STAT5 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D000093242:Interleukin-6 Inhibitors; C491590:Socs1 protein, mouse; C513811:diphlorethohydroxycarmalol; C577686:interleukin-6, mouse; C440499:lipopolysaccharide, Escherichia coli O111 B4