Prostaglandin E
Animals
Cell Line
Dermatitis, Atopic
/ genetics
Dinoprostone
/ metabolism
Disease Models, Animal
Down-Regulation
Female
Humans
Immunoglobulins
/ genetics
Inflammation
/ genetics
Interleukin-33
/ genetics
Keratinocytes
/ metabolism
Mice
Mice, Inbred BALB C
Mice, Knockout
Receptors, Cytokine
/ genetics
Receptors, Prostaglandin E, EP2 Subtype
/ metabolism
Signal Transduction
Skin
/ metabolism
IL-33
Prostaglandin E(2)
prostaglandin E(2) receptor
protease-activated receptor 2
thymic stromal lymphopoietin
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
24
02
2019
revised:
08
06
2019
accepted:
25
06
2019
pubmed:
14
7
2019
medline:
17
6
2020
entrez:
14
7
2019
Statut:
ppublish
Résumé
Atopic dermatitis (AD) is a common and chronic inflammatory skin disease of type 2 immunity. Keratinocyte-derived cytokines, including thymic stromal lymphopoietin (TSLP) and IL-33, are considered to induce the development of AD. Production of prostanoids, a family of lipid mediators, is increased in AD lesions. However, their physiologic functions remain to be clarified. We sought to elucidate the functions of prostanoids in the development of AD. The roles of prostanoids were investigated in a mouse model of AD induced by repeated application of hapten and PAM212, a keratinocyte cell line. Application of indomethacin, which blocks prostanoid synthesis, leads to enhanced TSLP and IL-33 production in the skin, increased serum IgE levels, and exacerbation of skin inflammation in this AD model. The skin inflammation was attenuated in TSLP receptor-deficient mice but not in IL-33-deficient mice, and the indomethacin-enhanced type 2 immune responses were abolished in TSLP receptor-deficient mice. Indomethacin increased protease-activated receptor 2-mediated TSLP production in keratinocytes in vitro, and prostaglandin E Prostaglandin E
Sections du résumé
BACKGROUND
Atopic dermatitis (AD) is a common and chronic inflammatory skin disease of type 2 immunity. Keratinocyte-derived cytokines, including thymic stromal lymphopoietin (TSLP) and IL-33, are considered to induce the development of AD. Production of prostanoids, a family of lipid mediators, is increased in AD lesions. However, their physiologic functions remain to be clarified.
OBJECTIVES
We sought to elucidate the functions of prostanoids in the development of AD.
METHODS
The roles of prostanoids were investigated in a mouse model of AD induced by repeated application of hapten and PAM212, a keratinocyte cell line.
RESULTS
Application of indomethacin, which blocks prostanoid synthesis, leads to enhanced TSLP and IL-33 production in the skin, increased serum IgE levels, and exacerbation of skin inflammation in this AD model. The skin inflammation was attenuated in TSLP receptor-deficient mice but not in IL-33-deficient mice, and the indomethacin-enhanced type 2 immune responses were abolished in TSLP receptor-deficient mice. Indomethacin increased protease-activated receptor 2-mediated TSLP production in keratinocytes in vitro, and prostaglandin E
CONCLUSION
Prostaglandin E
Identifiants
pubmed: 31301371
pii: S0091-6749(19)30904-2
doi: 10.1016/j.jaci.2019.06.036
pii:
doi:
Substances chimiques
Immunoglobulins
0
Interleukin-33
0
Receptors, Cytokine
0
Receptors, Prostaglandin E, EP2 Subtype
0
Tslpr protein, mouse
0
Dinoprostone
K7Q1JQR04M
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1265-1273.e9Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.