Anthralin decreases keratinocyte TGF-alpha expression and EGF-receptor binding in vitro.
Anthralin is an effective topical treatment for active psoriasis; however, its mechanism of action is unknown. Both TGF-alpha and its receptor, the EGF receptor, are overexpressed in active psoriatic plaques and might, therefore, play a role in psoriatic epidermal hyperplasia. In order to assess whether anthralin might act via alteration of this growth factor pathway, we examined the in vitro effects of pharmacologic concentrations of anthralin on cultured normal human keratinocytes. Keratinocyte proliferation was inhibited by 98% at an anthralin concentration of 10 ng/ml. In contrast, lymphocyte proliferation was inhibited by only 50% at an anthralin concentration of 10 micrograms/ml. Anthralin treatment did not induce cell-cycle-specific growth arrest as assessed by flow-cytometric analysis of acridine-orange-stained keratinocytes. Northern analysis of anthralin-treated keratinocytes demonstrated a marked decrease in TGF-alpha mRNA expression. Anthralin-treated keratinocytes showed decreased binding of 125I-EGF and 125I-IGF-I to their respective receptors, but EGF receptor binding was inhibited to a greater extent. Anthralin decreased ligand-binding affinity and cell-surface numbers of EGF receptors as assessed by Scatchard analysis of 125I-EGF binding to anthralin-treated keratinocytes. These results indicate that anthralin alters components of the EGF receptor pathway in cultured keratinocytes and that these effects might contribute to the clinical efficacy of anthralin in the treatment of active psoriasis.
Gottlieb
A B
AB
Laboratory for Investigative Dermatology, Rockefeller University, New York 10021-6399.
Khandke
L
L
Krane
J F
JF
Staiano-Coico
L
L
Ashinoff
R
R
Krueger
J G
JG
D000875:Anthralin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015603:Keratinocytes / Q000737:chemistry* / Q000166:cytology / Q000648:ultrastructure*; D011565:Psoriasis / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects; D017451:Receptors, Somatomedin; D016211:Transforming Growth Factor alpha / Q000032:analysis* / Q000037:antagonists & inhibitors
D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D016211:Transforming Growth Factor alpha; D007334:Insulin-Like Growth Factor I; D066246:ErbB Receptors; D000875:Anthralin