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

Stefen A. Boehme*, Karin Franz-Bacon, Edward P. Chen, Roman Šášik, L. James Sprague, Tai Wei Ly, Gary Hardiman, Kevin B. Bacon

*Corresponding author for this work

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

A FITC-induced allergic contact hypersensitivity model was used to investigate the role that the prostaglandin D2 receptor-chemoattractant receptor-homologous molecule expressed on Th2 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.

Original languageEnglish
Pages (from-to)81-93
Number of pages13
JournalInternational immunology
Volume21
Issue number1
DOIs
Publication statusPublished - 05 Jan 2009
Externally publishedYes

Keywords

  • Allergy
  • CRTH2
  • Inflammation
  • Prostaglandin D
  • Skin

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation'. Together they form a unique fingerprint.

  • Cite this

    Boehme, S. A., Franz-Bacon, K., Chen, E. P., Šášik, R., Sprague, L. J., Ly, T. W., Hardiman, G., & Bacon, K. B. (2009). A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation. International immunology, 21(1), 81-93. https://doi.org/10.1093/intimm/dxn127