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Triptolide Inhibits IFN‐γ Signaling via the Jak/STAT Pathway in HaCaT Keratinocytes
Author(s) -
Hongqin Tu,
Xinyu Li,
Heng Gu,
Lanfang Xu,
Yongfang Wang,
Shasha Song
Publication year - 2011
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.3471
Subject(s) - triptolide , hacat , stat protein , tripterygium wilfordii , signal transduction , keratinocyte , janus kinase , cytokine , stat1 , jak stat signaling pathway , pharmacology , medicine , chemistry , cell culture , cancer research , biology , microbiology and biotechnology , immunology , stat3 , apoptosis , biochemistry , tyrosine kinase , pathology , alternative medicine , genetics
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 (IC 50 = 1.37 × 10 −8 m ), pJak2 (IC 50 = 2.82 × 10 −9 m ) and pSTAT1 (IC 50 = 1.29 × 10 −9 m ) in HaCaT cells. The expression of SOCS1 was up‐regulated (ED 50 = 3.32 × 10 −11 m ). Triptolide also significantly reduced the expression of ICAM‐1 on the HaCaT cell surface (IC 50 = 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. Copyright © 2011 John Wiley & Sons, Ltd.