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          Institute: MPI für molekulare Biomedizin     Collection: Publikationen molekulare Biomedizin     Display Documents



  history
ID: 123169.0, MPI für molekulare Biomedizin / Publikationen molekulare Biomedizin
Proinflammatory role of proteinase-activated receptor-2 in humans and mice during cutaneous inflammation in vivo
Authors:Seeliger, S.; Derian, C. K.; Vergnolle, N.; Bunnett, N. W.; Nawroth, R.; Schmelz, M.; Von Der Weid, P. Y.; Buddenkotte, J.; Sunderkotter, C.; Metze, D.; Andrade-Gordon, P.; Harms, E.; Vestweber, D.; Luger, T. A.; Steinhoff, M.
Language:English
Date of Publication (YYYY-MM-DD):2003-10
Title of Journal:FASEB Journal
Journal Abbrev.:FASEB J
Volume:17
Issue / Number:13
Start Page:1871
End Page:1885
Review Status:not specified
Audience:Not Specified
Abstract / Description:Proteinase-activated receptor-2 belongs to a new subfamily of G-protein-coupled receptors. Its precise role during inflammation and the underlying mechanisms is still unclear. Our study establishes that PAR-2 plays a direct proinflammatory role during cutaneous inflammation in mice and humans in vivo. In a model of experimentally induced allergic (ACD) and toxic (ICD) contact dermatitis (CD) we show that ear swelling responses, plasma extravasation, and leucocyte adherence were significantly attenuated in PAR-2 null mutant (PAR-2-/-) mice compared with wild-type (PAR-2+/+) mice, especially at early stages. The proinflammatory effects by PAR-2 activation were significantly diminished using nitric oxide-synthase inhibitors, while NF-kappaB and neuropeptides appear to play a minor role in these mechanisms. PAR-2-mediated up-regulation of E-selectin and cell adhesion molecule ICAM-1; enhanced plasma extravasation was observed in humans and mice and of interleukin-6 in mice in vivo. Thus, PAR-2 may be a beneficial therapeutic target for the treatment of inflammatory skin diseases.
Free Keywords:Adolescent
; Adult
; Animals
; Capillary Permeability
; Cell Adhesion
; Dermatitis/*immunology
; Dermatitis, Allergic Contact/immunology
; Dermatitis, Contact/immunology/pathology
; Dermis/pathology
; E-Selectin/metabolism
; Edema/etiology/pathology
; Human
; Intercellular Adhesion Molecule-1/metabolism
; Leukocytes/immunology
; Mice
; Mice, Inbred C57BL
; Mice, Knockout
; Middle Aged
; Nitric Oxide/physiology
; Oligopeptides/pharmacology
; Receptor, PAR-2
; Receptors, Thrombin/agonists/*physiology
; Skin/blood supply/drug effects/immunology
; Support, Non-U.S. Gov't
; Support, U.S. Gov't, P.H.S.
; Up-Regulation
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für molekulare Biomedizin
Identifiers:URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=... [ID No:1]
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