Antagonism of Epidermal Growth Factor Receptor Tyrosine Kinase Ameliorates the Psoriatic Phenotype in Organ-Cultured Skin

Vol. 18, No. 3, 2005

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Original Paper

Antagonism of Epidermal Growth Factor Receptor Tyrosine Kinase Ameliorates the Psoriatic Phenotype in Organ-Cultured Skin
J. Varani^a, H. Lateef^a, K. Fay^a, J.T. Elder^b

Departments of
^aPathology and
^bDermatology, The University of Michigan Medical School, Ann Arbor, Mich., USA

Address of Corresponding Author

Skin Pharmacol Physiol 2005;18:123-131 (DOI: 10.1159/000084909)

Key Words

Psoriasis
Epidermal growth factor
Receptor tyrosine kinase (EGF-RTK) antagonist
Keratinocytes
Fibroblasts
Skin organ culture
Matrix metalloproteinases
Type I procollagen

Abstract

Psoriatic plaque skin incubated for eight days in organ culture in the presence of a potent epidermal growth factor (EGF) receptor tyrosine kinase (RTK) antagonist reverted to a more normal histological appearance, while untreated psoriatic plaque skin retained histological features associated with the psoriatic phenotype. In concomitant studies it was shown that the EGF-RTK antagonist had no significant effect on histological features of non-psoriatic skin and no effect on dermal function, i.e. elaboration of both type I procollagen and matrix metalloproteinase-1 (MMP-1; interstitial collagenase). When human epidermal keratinocytes were treated with the EGF-RTK antagonist in monolayer culture, growth inhibition was seen (ED₅₀ = approximately 0.06 µM). When dermal fibroblasts were exposed to the EGF-RTK antagonist in monolayer culture, proliferation, MMP-1 and type I procollagen production were essentially unaffected at concentrations which interfered with keratinocyte growth (up to 1 µM). The capacity of the EGF-RTK antagonist to modulate the histological features of psoriatic skin in organ culture under conditions in which normal skin architecture and dermal function are largely unaffected suggests a potential for anti-psoriatic therapy.

Author Contacts

James Varani, PhD
Department of Pathology, The University of Michigan
1301 Catherine Road/Box 0602
Ann Arbor, MI 48109 (USA)
Tel. +1 734 615 0298, Fax +1 734 763 6476, E-Mail varani@umich.edu

Article Information

Received: July 5, 2004
Accepted after revision: November 19, 2004
Number of Print Pages : 9
Number of Figures : 6, Number of Tables : 1, Number of References : 36

Medline Abstract (ID 15897684)

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