Document Detail


Triptolide inhibits IFN-γ signaling via the Jak/STAT pathway in HaCaT keratinocytes.
MedLine Citation:
PMID:  21433155     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Interferon-gamma (IFN-γ) signaling in keratinocytes plays an important role in IFN-γ-mediated skin inflammation involved in psoriasis. Blocking IFN-γ signal transduction in keratinocytes could be a strategy for controlling inflammatory skin disorders. Tripterygium wilfordii Hook. F. (T. wilfordii) has been used effectively in psoriasis treatment in China. Its therapeutic mechanism on IFN-γ-dependent inflammation has not been elucidated. Triptolide is one of main components of T. wilfordii's antiinflammatory and immune effects. This study aimed to explore the effects of triptolide on an rhIFN-γ-stimulated human keratinocyte cell line (HaCaT) in culture. The expression of IFN-γ receptor α (IFN-γRα), phospho-Janus kinase2 (pJak2), phospho-signal transducer and activator of transcription 1 (pSTAT1) and suppressor of cytokine signaling 1 (SOCS1) was detected by western blotting. The expression of intercellular adhesion molecule-1 (ICAM-1) on the HaCaT cell surface was determined by cell-surface ELISA. The results demonstrated that triptolide inhibited the expression of IFN-γRα (IC₅₀  = 1.37 × 10⁻⁸ M), pJak2 (IC₅₀  = 2.82 × 10⁻⁹ M) and pSTAT1 (IC₅₀  = 1.29 × 10⁻⁹ M) in HaCaT cells. The expression of SOCS1 was up-regulated (ED₅₀  = 3.32 × 10⁻¹¹  M). Triptolide also significantly reduced the expression of ICAM-1 on the HaCaT cell surface (IC₅₀  = 5.82 × 10⁻¹⁰ M). This study suggests that triptolide may contribute to the therapeutic value of T. wilfordii by modulating the IFN-γ signal pathway in IFN-γ-dependent skin inflammatory diseases, including psoriasis.
Authors:
Tu Hongqin; Li Xinyu; Gu Heng; Xu Lanfang; Wang Yongfang; Song Shasha
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Publication Detail:
Type:  Journal Article     Date:  2011-03-24
Journal Detail:
Title:  Phytotherapy research : PTR     Volume:  25     ISSN:  1099-1573     ISO Abbreviation:  Phytother Res     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-10-24     Completed Date:  2012-02-22     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  8904486     Medline TA:  Phytother Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  1678-85     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 John Wiley & Sons, Ltd.
Affiliation:
Department of Pharmacology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
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MeSH Terms
Descriptor/Qualifier:
Cell Line
Cell Survival
Diterpenes / pharmacology*
Epoxy Compounds / pharmacology
Humans
Intercellular Adhesion Molecule-1 / metabolism
Interferon-gamma / metabolism*
Janus Kinase 2 / metabolism
Keratinocytes / drug effects*,  metabolism
Phenanthrenes / pharmacology*
Phosphorylation
Receptors, Interferon / metabolism
STAT1 Transcription Factor / metabolism
Signal Transduction / drug effects*
Suppressor of Cytokine Signaling Proteins / metabolism
Tripterygium / chemistry
Chemical
Reg. No./Substance:
0/Diterpenes; 0/Epoxy Compounds; 0/Phenanthrenes; 0/Receptors, Interferon; 0/SOCS1 protein, human; 0/STAT1 Transcription Factor; 0/STAT1 protein, human; 0/Suppressor of Cytokine Signaling Proteins; 0/interferon gamma receptor; 126547-89-5/Intercellular Adhesion Molecule-1; 38748-32-2/triptolide; 82115-62-6/Interferon-gamma; EC 2.7.10.1/Janus Kinase 2; EC 2.7.10.2/JAK2 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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