Back to Search
Start Over
Inhibiting glycogen synthase kinase-3 decreases 12-O-tetradecanoylphorbol-13-acetate-induced interferon-γ-mediated skin inflammation
- Source :
- The Journal of pharmacology and experimental therapeutics. 343(1)
- Publication Year :
- 2012
-
Abstract
- Glycogen synthase kinase-3 (GSK-3) facilitates interferon (IFN)-γ signaling. Because IFN-γ is involved in inflammatory skin diseases, such as psoriasis, the aim of this study was to investigate the pathogenic role of GSK-3 in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced IFN-γ-mediated ear skin inflammation. TPA (3 μg per ear) induced acute skin inflammation in the ears of C57BL/6 mice, including edema, infiltration of granulocytes but not T cells, and IFN-γ receptor 1-mediated deregulation of intercellular adhesion molecule 1 (CD54). TPA/IFN-γ induced GSK-3 activation, which in turn activated signal transducer and activator of transcription 1. Inhibiting GSK-3 pharmacologically, by administering 6-bromoindirubin-3′-oxime (1.5 μg per ear), and genetically, with lentiviral-based short-hairpin RNA, reduced TPA-induced acute skin inflammation but not T-cell infiltration. It is noteworthy that inhibiting GSK-3 decreased TPA-induced IFN-γ production and the nuclear translocation of T-box transcription factor Tbx21, a transcription factor of IFN-γ, in CD3-positive T cells. In chronic TPA-induced skin inflammation, inhibiting GSK-3 attenuated epidermis hyperproliferation and dermis angiogenesis. These results demonstrate the dual role of GSK-3 in TPA-induced skin inflammation that is not only to facilitate IFN-γ signaling but also to regulate IFN-γ production. Inhibiting GSK-3 may be a potential treatment strategy for preventing such effects.
- Subjects :
- medicine.medical_specialty
Indoles
Intercellular Adhesion Molecule-1
Inflammation
Dermatitis
12-O-Tetradecanoylphorbol-13-acetate
Cell Line
chemistry.chemical_compound
Glycogen Synthase Kinase 3
Interferon-gamma
Mice
Interferon
GSK-3
Internal medicine
Oximes
Medicine
Animals
Humans
Glycogen synthase
Transcription factor
Receptors, Interferon
Pharmacology
Mice, Knockout
integumentary system
biology
business.industry
Mice, Inbred C57BL
Endocrinology
chemistry
STAT protein
Cancer research
biology.protein
Molecular Medicine
Tetradecanoylphorbol Acetate
medicine.symptom
business
medicine.drug
Subjects
Details
- ISSN :
- 15210103
- Volume :
- 343
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- The Journal of pharmacology and experimental therapeutics
- Accession number :
- edsair.doi.dedup.....6c9eeac4863ec62e4f44b277a2561ece