A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation

A FITC-induced allergic contact hypersensitivity model was used to investigate the role that the prostaglandin D(2) receptor–chemoattractant receptor-homologous molecule expressed on T(h)2 cells (CRTH2) plays in modulating cutaneous inflammation. Our results show that inhibition of CRTH2, achieved v...

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Päätekijät: Boehme, Stefen A., Franz-Bacon, Karin, Chen, Edward P., Šášik, Roman, Sprague, L. James, Ly, Tai Wei, Hardiman, Gary, Bacon, Kevin B.
Aineistotyyppi: Artikkeli
Kieli:English
Julkaistu: Oxford University Press 2009
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Featured Article of the Month
Linkit:https://ncbi.nlm.nih.gov/pmc/articles/PMC2638841/
https://ncbi.nlm.nih.gov/pubmed/19066314
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1093/intimm/dxn127
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spelling pubmed-26388412010-01-01 A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation Boehme, Stefen A. Franz-Bacon, Karin Chen, Edward P. Šášik, Roman Sprague, L. James Ly, Tai Wei Hardiman, Gary Bacon, Kevin B. Int Immunol Featured Article of the Month A FITC-induced allergic contact hypersensitivity model was used to investigate the role that the prostaglandin D(2) receptor–chemoattractant receptor-homologous molecule expressed on T(h)2 cells (CRTH2) plays in modulating cutaneous inflammation. Our results show that inhibition of CRTH2, achieved via administration of a potent, small molecule antagonist, Compound A (Cmpd A), effectively blocked edema formation and greatly reduced the inflammatory infiltrate and skin pathology observed in drug vehicle-treated animals. Gene expression analysis revealed that Cmpd A administration down-regulated the transcription of a wide range of pro-inflammatory mediators. This correlated with decreases in cytokine and chemokine protein levels, notably IL-4, IL-1β, tumor necrosis factor-α, transforming growth factor-β, GRO-α, MIP-2 and thymic stromal lymphopoietin (TSLP) in FITC-challenged ears. The administration of an anti-TSLP-neutralizing antibody was only partially effective in lowering the FITC-induced inflammatory infiltrate and cytokine production compared with the CRTH2 antagonist. Taken together, these data suggest that blockade of CRTH2 inhibits multiple pathways leading to cutaneous inflammation in this model. This suggests that CRTH2 antagonism may be a viable route for therapeutic intervention in allergic skin diseases, such as atopic dermatitis. Oxford University Press 2009-01 2008-12-09 /pmc/articles/PMC2638841/ /pubmed/19066314 http://dx.doi.org/10.1093/intimm/dxn127 Text en © The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
institution US National Library of Medicine
collection PubMed Central
language English
format Article
topic Featured Article of the Month
spellingShingle Featured Article of the Month
Boehme, Stefen A.
Franz-Bacon, Karin
Chen, Edward P.
Šášik, Roman
Sprague, L. James
Ly, Tai Wei
Hardiman, Gary
Bacon, Kevin B.
A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation
description A FITC-induced allergic contact hypersensitivity model was used to investigate the role that the prostaglandin D(2) receptor–chemoattractant receptor-homologous molecule expressed on T(h)2 cells (CRTH2) plays in modulating cutaneous inflammation. Our results show that inhibition of CRTH2, achieved via administration of a potent, small molecule antagonist, Compound A (Cmpd A), effectively blocked edema formation and greatly reduced the inflammatory infiltrate and skin pathology observed in drug vehicle-treated animals. Gene expression analysis revealed that Cmpd A administration down-regulated the transcription of a wide range of pro-inflammatory mediators. This correlated with decreases in cytokine and chemokine protein levels, notably IL-4, IL-1β, tumor necrosis factor-α, transforming growth factor-β, GRO-α, MIP-2 and thymic stromal lymphopoietin (TSLP) in FITC-challenged ears. The administration of an anti-TSLP-neutralizing antibody was only partially effective in lowering the FITC-induced inflammatory infiltrate and cytokine production compared with the CRTH2 antagonist. Taken together, these data suggest that blockade of CRTH2 inhibits multiple pathways leading to cutaneous inflammation in this model. This suggests that CRTH2 antagonism may be a viable route for therapeutic intervention in allergic skin diseases, such as atopic dermatitis.
author Boehme, Stefen A.
Franz-Bacon, Karin
Chen, Edward P.
Šášik, Roman
Sprague, L. James
Ly, Tai Wei
Hardiman, Gary
Bacon, Kevin B.
author_facet Boehme, Stefen A.
Franz-Bacon, Karin
Chen, Edward P.
Šášik, Roman
Sprague, L. James
Ly, Tai Wei
Hardiman, Gary
Bacon, Kevin B.
author_sort Boehme, Stefen A.
title A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation
title_short A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation
title_full A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation
title_fullStr A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation
title_full_unstemmed A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation
title_sort small molecule crth2 antagonist inhibits fitc-induced allergic cutaneous inflammation
publisher Oxford University Press
publisher_facet Oxford University Press
publishDate 2009
url https://ncbi.nlm.nih.gov/pmc/articles/PMC2638841/
https://ncbi.nlm.nih.gov/pubmed/19066314
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1093/intimm/dxn127
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