Constitutive expression of aryl hydrocarbon receptor in keratinocytes causes inflammatory skin lesions

Masafumi Tauchi, Azumi Hida, Takaaki Negishi, Fumiki Katsuoka, Shuhei Noda, Junsei Mimura, Tomonori Hosoya, Akinori Yanaka, Hiroyuki Aburatani, Yoshiaki Fujii-Kuriyama, Hozumi Motohashi, Masayuki Yamamoto

Research output: Contribution to journalArticlepeer-review

112 Citations (Scopus)

Abstract

Occupational and environmental exposure to polycyclic aromatic hydrocarbons (PAHs) has been suggested to provoke inflammatory and/or allergic disorders, including asthma, rhinitis, and dermatitis. The molecular mechanisms of this PAH-mediated inflammation remain to be clarified. Previous studies implied the involvement of PAHs as irritants and allergens, with the reactive oxygen species generated from the oxygenated PAHs believed to be an exacerbating factor. It is also possible that PAHs contribute to the pathogenesis through activation of aryl-hydrocarbon receptor (AhR)-mediated transcription, since PAHs are potent inducers of the AhR. To address this point, we generated transgenic mouse lines expressing the constitutive active form of the AhR in keratinocytes. In these lines of mice, the AhR activity was constitutively enhanced in the absence of ligands, so that any other direct elects of PAHs and their metabolites could be ignored. At birth, these transgenic mice were normal, but severe skin lesions with itching developed postnatally. The skin lesions were accompanied by inflammation and immunological imbalance and resembled typical atopic dermatitis. We demonstrate that constitutive activation of the AhR pathway causes inflammatory skin lesions and suggests a new mechanism for the exacerbation of inflammatory diseases after exposure to occupational and environmental xenobiotics.

Original languageEnglish
Pages (from-to)9360-9368
Number of pages9
JournalMolecular and cellular biology
Volume25
Issue number21
DOIs
Publication statusPublished - 2005 Nov

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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