IL-1 alpha-induced expression of ICAM-1 on cultured hyperproliferative keratinocytes: suppression by antipsoriatic dimethyl-fumarate.
BACKGROUND
In the psoriatic plaque both IL-1 dysregulation and ICAM-1 expression on keratinocytes have been previously described. Furthermore systemic administration of fumarates has been reported to be effective in psoriasis. We, therefore, studied the effect of dimethyl-fumarate ester (DMF) on the putative IL-1-induced ICAM-1 expression.


METHODS
Hyperproliferative human keratinocytes (HaCaT cell line) were incubated in 10 to 100 U/mL IL-1 alpha for 24 h with and without preincubation with 0.4-12.0 microM DMF: Expression of ICAM-1 was measured by a special ELISA-APAAP technique.


RESULTS
The exposure to IL-1 led to a significant dose-dependent induction of ICAM-1 expression of from 124 +/- 17 to 194 +/- 22% (control 100 +/- 12%), while proliferation remained unaltered. Pretreatment with > or = 4 microM DMF resulted in a distinct suppression of ICAM-1 expression and a slight decrease in proliferation.


CONCLUSIONS
The present results show that ICAM-1 expression on hyperproliferative keratinocytes may be triggered by IL-1 alpha and serve as a molecular target for antipsoriatic DMF.
Sebök
B
B
Department of Dermatology, University of Cologne, Germany.
Bonnekoh
B
B
Mahrle
G
G
D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D000069462:Dimethyl Fumarate; D004305:Dose-Response Relationship, Drug; D005650:Fumarates / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007375:Interleukin-1 / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology
D015815:Cell Adhesion Molecules; D005650:Fumarates; D007375:Interleukin-1; D018799:Intercellular Adhesion Molecule-1; D000069462:Dimethyl Fumarate