Blunted epidermal L-tryptophan metabolism in vitiligo affects immune response and ROS scavenging by Fenton chemistry, Part 2: Epidermal H 2O2/ONOO--mediated stress in vitiligo hampers indoleamine 2,3-dioxygenase and aryl hydrocarbon receptor-mediated immune response signaling

Download
  1. Get@NRC: Blunted epidermal L-tryptophan metabolism in vitiligo affects immune response and ROS scavenging by Fenton chemistry, Part 2: Epidermal H 2O2/ONOO--mediated stress in vitiligo hampers indoleamine 2,3-dioxygenase and aryl hydrocarbon receptor-mediated immune response signaling (Opens in a new window)
DOIResolve DOI: http://doi.org/10.1096/fj.11-201897
AuthorSearch for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for:
TypeArticle
Journal titleFASEB Journal
ISSN0892-6638
Volume26
Issue6
Pages24712485; # of pages: 15
Subjectaromatic hydrocarbon receptor; cyclooxygenase 2; cytochrome P450 1A1; hydrogen peroxide; indoleamine 2,3 dioxygenase; peroxynitrite; reactive oxygen metabolite; tryptophan; tryptophan hydroxylase; adult; article; clinical article; controlled study; Fenton reaction; Fourier transform mass spectrometry; human; immune response; in vitro study; in vivo study; mass spectrometry; priority journal; Raman spectrometry; regulatory T lymphocyte; stress; vitiligo; Computer Simulation; Epidermis; Humans; Hydrogen Peroxide; Indoleamine-Pyrrole 2,3,-Dioxygenase; Oxidative Stress; Peroxynitrous Acid; Receptors, Aryl Hydrocarbon; Signal Transduction; T-Lymphocytes, Regulatory; Tryptophan; Vitiligo
AbstractVitiligo is characterized by a mostly progressive loss of the inherited skin color. The cause of the disease is still unknown, despite accumulating in vivo and in vitro evidence of massive oxidative stress via hydrogen peroxide (H2O2) and peroxynitrite (ONOO-) in the skin of affected individuals. The most favored hypothesis is based on autoimmune mechanisms. Since depletion of the essential amino acid L-tryptophan (Trp) severely affects various immune responses, we here looked at Trp metabolism and signaling in these patients. Our in vivo and in vitro data revealed total absence of epidermal Trp hydroxylase activities and the presence of H 2O2/ONOO- deactivated indoleamine 2,3-dioxygenase. Aryl hydrocarbon receptor signaling is severely impaired despite the ligand (Trp dimer) being formed, as shown by mass spectrometry. Loss of this signal is supported by the absence of downstream signals (COX-2 and CYP1A1) as well as regulatory T-lymphocytes and by computer modeling. In vivo Fourier transform Raman spectroscopy confirmed the presence of Trp metabolites together with H2O2 supporting deprivation of the epidermal Trp pool by Fenton chemistry. Taken together, our data support a long-expressed role for in loco redox balance and a distinct immune response. These insights could open novel treatment strategies for this disease. © FASEB.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Biotechnology Research Institute (BRI-IRB)
Peer reviewedYes
NPARC number21269455
Export citationExport as RIS
Report a correctionReport a correction
Record identifiere5ac2ae4-360f-4662-856f-5520fbd07ea0
Record created2013-12-12
Record modified2016-05-09
Bookmark and share
  • Share this page with Facebook (Opens in a new window)
  • Share this page with Twitter (Opens in a new window)
  • Share this page with Google+ (Opens in a new window)
  • Share this page with Delicious (Opens in a new window)