Evidence for an altered protein kinase C (PKC) signaling pathway in psoriasis.
Treatment of normal primary human keratinocytes with phorbol 12-myristate 13-acetate (PMA) or phorbol 12-13 dibutyrate (PDBu) (100 ng/ml, 6-40 h) followed by two-dimensional (2-D) gel electrophoresis (isoelectric focusing) and microsequencing identified three polypeptides (phorbolin 1, M(r) = 19.9 kDa; phorbolin 2, M(r) = 19.7 kDa; and interleukin-1 (IL-1) receptor antagonist, IL-1ra, M(r) = 19.5 kDa) that are upregulated eight times or more by the phorbol esters and that are highly expressed in noncultured psoriatic keratinocytes. The response was not elicited by other effectors tested including second messengers (Bt2cAMP, Bt2cGMP), cytokines (basic fibroblast growth factor, transforming growth factor-alpha, IGF-II, tumor necrosis factor-alpha, and -beta, interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-3, IL-6, IL-7, IL-8, interferon-alpha, and -gamma), and other substances (Ca++, dexametasone, retinoic acid, lipopolysaccharides) and it was partially reversed by staurosporine, a strong inhibitor of protein kinase C. The results are taken to imply that the protein kinase C signaling pathway may be altered in psoriatic keratinocytes.
Rasmussen
H H
HH
Institute of Medical Biochemistry, Aarhus University, Denmark.
Celis
J E
JE
D000470:Alkaloids / Q000494:pharmacology; D002478:Cells, Cultured; D005470:Fluorometry; D006801:Humans; D007525:Isoelectric Focusing; D015603:Keratinocytes / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011565:Psoriasis / Q000378:metabolism*; D012016:Reference Values; D015398:Signal Transduction; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate