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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
1997-12-22
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pubmed:abstractText |
Protein kinase C (PKC) regulates keratinocyte growth and differentiation as well as inflammation in skin, processes which are abnormal in skin diseases such as psoriasis. 12-O-tetradecanoylphorbol-13-acetate (TPA) binds to and activates PKC. We investigated the effects of SCH 47112, a novel staurosporine derivative, which interacts with the catalytic domain of PKC, on TPA-induced inflammation and hyperplasia in hairless mouse skin and TPA-induced differentiation in cultured human keratinocytes. Dorsal mouse skin was treated with vehicle, TPA (2.0/ 2.5 nmol) or SCH 47112 followed by TPA. Epidermal thickness, and epidermal, upper dermal and deep dermal inflammation (assessed on an ordinal semiquantitative scale) were determined in biopsies taken 24 h and 48 h post-treatment. SCH 47112 (100 nmol) inhibited TPA-induced epidermal, upper dermal and deep dermal inflammation by 71%, 45% and 22%, respectively, at 24 h (n = 3, P < 0.05). TPA-induced epidermal hyperplasia was inhibited by SCH 47112 (400 nmol) by 38% at 48 h (n = 3, P < 0.05). In addition, in cultured human keratinocytes, SCH 47112 inhibited TPA induction of transglutaminase. I protein, which catalyzes the formation of crosslinked envelopes. These results indicate that SCH 47112 exhibits biological activity, inhibiting TPA-induced changes in hairless mouse skin in vivo and cultured human keratinocytes in vitro, and suggest that PKC inhibitors may have a therapeutic role in inflammatory skin diseases.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0340-3696
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
289
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
540-6
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9341975-Animals,
pubmed-meshheading:9341975-Anti-Inflammatory Agents,
pubmed-meshheading:9341975-Cells, Cultured,
pubmed-meshheading:9341975-Enzyme Inhibitors,
pubmed-meshheading:9341975-Epidermis,
pubmed-meshheading:9341975-Humans,
pubmed-meshheading:9341975-Hyperplasia,
pubmed-meshheading:9341975-Keratinocytes,
pubmed-meshheading:9341975-Male,
pubmed-meshheading:9341975-Mice,
pubmed-meshheading:9341975-Mice, Hairless,
pubmed-meshheading:9341975-Molecular Structure,
pubmed-meshheading:9341975-Protein Kinase C,
pubmed-meshheading:9341975-Staurosporine,
pubmed-meshheading:9341975-Tetradecanoylphorbol Acetate
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pubmed:year |
1997
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pubmed:articleTitle |
SCH 47112, a novel staurosporine derivative, inhibits 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and epidermal hyperplasia in hairless mouse skin.
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pubmed:affiliation |
Department of Dermatology, University of Michigan Medical School, Ann Arbor 48109-0609, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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