ISSN:
1432-069X
Keywords:
Key words SCH 47112
;
TPA
;
Inflammation
;
Epidermal hyperplasia
;
Mouse skin
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s004030050236
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