The aryl hydrocarbon receptor (AhR) as an environmental stress sensor and regulator of skin barrier function: Molecular mechanisms and therapeutic opportunities

Rebecca Justiniano, Georg T Wondrak

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

The aryl hydrocarbon receptor (AhR) is a transcription factor responsive to both xenobiotic and endogenous ligands involved in skin barrier adaptations in response to environmental and endogenous stressors. Due to the fundamental role that AhR-controlled signaling plays in skin barrier formation, homeostasis, resilience to environmental stressors, and damage repair, AhR-directed pharmacological strategies that aim at AhR-orchestrated signaling for anti-inflammatory, immune-modulatory, cancer chemopreventive, and barrier enhancing intervention show great therapeutic promise, delivering unique patient-directed benefit by targeting specific skin pathologies (including psoriasis, atopic dermatitis, seborrheic dermatitis, and solar radiation-induced skin photodamage) that have remained elusive and difficult to treat. The ever expanding and accessible range of chemically diverse physiological and synthetic AhR-modulators that differ with regard to pharmacokinetic and pharmacodynamic profile, AhR-directed potency, metabolic stability, and off-target effects through engagement of other signaling pathways provides a versatile and accessible compound platform of prototype agents and therapeutic leads for experimental intervention through AhR engagement, potentially representing breakthrough therapeutics that can quickly be optimized, developed, and formulated into novel AhR-directed cutaneous therapeutic entities.

Original languageEnglish (US)
Title of host publicationSkin Stress Response Pathways
Subtitle of host publicationEnvironmental Factors and Molecular Opportunities
PublisherSpringer International Publishing
Pages325-359
Number of pages35
ISBN (Electronic)9783319431574
ISBN (Print)9783319431550
DOIs
Publication statusPublished - Jan 1 2016

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Keywords

  • Aryl hydrocarbon receptor
  • Atopic dermatitis
  • Cinnabarinic acid
  • CYP1A1
  • FICZ
  • ITE
  • Ketoconazole
  • Kynurenine
  • LINE-1
  • Malassezin
  • Melanoma
  • Nrf2
  • Photocarcinogenesis
  • Psoriasis
  • Seborrheic dermatitis
  • TCDD
  • Tryptophan
  • UVA
  • UVB
  • Vitiligo

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Justiniano, R., & Wondrak, G. T. (2016). The aryl hydrocarbon receptor (AhR) as an environmental stress sensor and regulator of skin barrier function: Molecular mechanisms and therapeutic opportunities. In Skin Stress Response Pathways: Environmental Factors and Molecular Opportunities (pp. 325-359). Springer International Publishing. https://doi.org/10.1007/978-3-319-43157-4_16