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

Autor: Jin Won Hyun, Dong Hwan Koo, Nam Ho Lee, Mi Hee Ko, Hee Kyoung Kang, Eun Sook Yoo, Young Sang Koh, Gyeoung Jin Kang, Sang Chul Han, Na Jin Kang
Rok vydání: 2015
Předmět:
Lipopolysaccharides
Pharmaceutical Science
Suppressor of Cytokine Signaling Proteins
NF-κB
Mice
chemistry.chemical_compound
Drug Discovery
STAT5 Transcription Factor
lcsh:QH301-705.5
Pharmacology
Toxicology and Pharmaceutics (miscellaneous)
STAT5
Skin
Mice
Inbred BALB C
Anti-Inflammatory Agents
Non-Steroidal
NF-kappa B
JAK-STAT signaling pathway
Jak-STAT
SOCS
Specific Pathogen-Free Organisms
Cell biology
Biochemistry
diphlorethohydroxycarmalol (DPHC)
Female
Tumor necrosis factor alpha
Heterocyclic Compounds
3-Ring
LPS
Biology
Administration
Cutaneous
Phaeophyta
Article
Dermatitis
Atopic
Suppressor of Cytokine Signaling 1 Protein
Downregulation and upregulation
Republic of Korea
Animals
Interleukin 6
IL-6
Pacific Ocean
Dose-Response Relationship
Drug
Interleukin-6
Suppressor of cytokine signaling 1
Macrophages
RAW 264.7 Cells
Gene Expression Regulation
lcsh:Biology (General)
chemistry
inflammation
biology.protein
Janus kinase
Zdroj: Marine Drugs
Volume 13
Issue 4
Pages 2141-2157
Marine Drugs, Vol 13, Iss 4, Pp 2141-2157 (2015)
MARINE DRUGS(13): 4
ISSN: 1660-3397
DOI: 10.3390/md13042141
Popis: 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-alpha) induced by LPS. DPHC (12.5 and 100 mu M) suppressed the phosphorylation and the nuclear translocation of NF-kappaB (NF-kappa B), 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 mu M. Furthermore, N-tosyl-l-phenylalanine chloromethyl ketone (TPCK) (a specific NF-kappa B inhibitor) and JI (a specific Jak2 inhibitor) reduced the production of IL-6, but not that of tumor necrosis factor-alpha (TNF-alpha) in LPS-stimulated RAW 264.7 macrophages. These findings demonstrate that DPHC inhibits IL-6 production via the downregulation of NF-kappa B and Jak2-STAT5 pathway and upregulation of SOCS1.
Databáze: OpenAIRE
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