Novel steroid derivative modulates gene expression of cytokines and growth regulators.
Topical steroid treatment is a common therapy for psoriasis. Steroids are known to bind to specific cytoplasmic receptors and to influence gene expression. We investigated the effects of the novel steroid derivative mometasone furoate on the expression of putative target genes in normal human epidermal cells (KC). Gene expression was measured by semiquantitative mRNA-PCR. In addition, cytokine receptor characteristics were assessed by ligand binding studies. We found a dose-dependent downregulation of proinflammatory mediators (IL-8, TNF alpha). Genes involved in growth regulation (HER-2, p53) were also modulated. IL-8 binding to KC was inhibited. We conclude that modulation of the expression of cytokine, cytokine receptor and growth factor genes may contribute to the antipsoriatic action of steroids.
Michel
G
G
Department of Dermatology, University of Düsseldorf, Germany.
Nowok
K
K
Beetz
A
A
Ried
C
C
Kemény
L
L
Ruzicka
T
T
D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001623:Betamethasone / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects; D016207:Cytokines / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D000068656:Mometasone Furoate; D016133:Polymerase Chain Reaction; D011244:Pregnadienediols / Q000494:pharmacology; D011565:Psoriasis; D012333:RNA, Messenger / Q000096:biosynthesis; D018121:Receptors, Cytokine / Q000235:genetics*; D013256:Steroids / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D011244:Pregnadienediols; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D013256:Steroids; D000068656:Mometasone Furoate; D001623:Betamethasone; D006854:Hydrocortisone