Novel inhibitory effect of a lysophosphatidic acid 2 agonist on allergen-driven airway inflammation

Sara A. Knowlden, Sara E. Hillman, Timothy J. Chapman, Renukadevi Patil, Duane Miller, Gabor Tigyi, Steve N. Georas

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Lysophosphatidic acid (LPA) is a pleiotropic lipid signaling molecule associated with asthma pathobiology. LPA elicits its effects by binding to at least six known cell surfaceGprotein-coupled receptors (LPA1-6) that are expressed in the lung in a cell type-specific manner. LPA2 in particular has emerged as an attractive therapeutic target in asthma because it appears to transduce inhibitory or cell-protective signals. We studied a novel and specific small molecule LPA2 agonist (2-[4-(1,3-dioxo-1H,3H-benzoisoquinolin-2-yl)butylsulfamoyl] benzoic acid [DBIBB]) in a mousemodel of house dustmite-induced allergic airway inflammation. Mice injected with DBIBB developed significantly less airway and lung inflammation compared with vehicle-treated controls. Levels of lung Th2 cytokines were also significantly attenuated by DBIBB. We conclude that pharmacologic activation of LPA2attenuatesTh2-driven allergic airway inflammation in a mouse model of asthma. Targeting LPA receptor signaling holds therapeutic promise in allergic asthma.

Original languageEnglish (US)
Pages (from-to)402-409
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume54
Issue number3
DOIs
StatePublished - Mar 1 2016

Fingerprint

Lysophosphatidic Acid Receptors
Allergens
Asthma
Inflammation
Molecules
Lung
Chemical activation
Cytokines
Lipids
Pneumonia
lysophosphatidic acid
Therapeutics

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Novel inhibitory effect of a lysophosphatidic acid 2 agonist on allergen-driven airway inflammation. / Knowlden, Sara A.; Hillman, Sara E.; Chapman, Timothy J.; Patil, Renukadevi; Miller, Duane; Tigyi, Gabor; Georas, Steve N.

In: American journal of respiratory cell and molecular biology, Vol. 54, No. 3, 01.03.2016, p. 402-409.

Research output: Contribution to journalArticle

Knowlden, Sara A. ; Hillman, Sara E. ; Chapman, Timothy J. ; Patil, Renukadevi ; Miller, Duane ; Tigyi, Gabor ; Georas, Steve N. / Novel inhibitory effect of a lysophosphatidic acid 2 agonist on allergen-driven airway inflammation. In: American journal of respiratory cell and molecular biology. 2016 ; Vol. 54, No. 3. pp. 402-409.
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