Anti-psoriatic drug anthralin activates JNK via lipid peroxidation: Mononuclear cells are more sensitive than keratinocytes

Dominik Peus, Astrid Beyerle, Heike L. Rittner, Markus Pott, Alexander Meves, Cornelia Weyand, Mark R. Pittelkow

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Anthralin is a widely used, topical therapy for psoriasis. Anti- proliferative and anti-inflammatory properties of anthralin have been identified. Little is known, however, about differential sensitivities of targeted cell types and specific mechanisms of signaling pathway activation. We demonstrate that anthralin exerts potent effects on keratinocytes and mononuclear cells through strong induction of lipid peroxidation and JNK activation, a stress-induced signal transduction pathway. Lipid peroxidation was observed rapidly and half-maximal levels of lipid peroxidation were reached at a 10-fold lower concentration of anthralin for peripheral blood mononuclear cells vs normal keratinocytes. JNK activation was detected in peripheral blood mononuclear cells at a 40-fold lower anthralin dose compared with kerarinocytes. For both cell types, selected inhibitors of lipid peroxidation prevented JNK activation. This study demonstrates that mononuclear leukocytes are markedly more sensitive than keratinocytes to anthralin-induced lipid peroxidation and JNK activation. We identify anthralin as a novel and potent inducer of JNK activation and demonstrate that this process is mediated, at least in part, by lipid peroxidation which is among the earliest and most proximate, membrane-related responses to anthralin yet described.

Original languageEnglish (US)
Pages (from-to)688-692
Number of pages5
JournalJournal of Investigative Dermatology
Volume114
Issue number4
DOIs
StatePublished - Jan 1 2000

Keywords

  • Anthralin
  • C-jun-N-terminal protein kinase
  • Keratinocytes
  • Lipid peroxidation
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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