title: Novel Inhibitory Effect of a Lysophosphatidic Acid 2 Agonist on Allergen-Driven Airway Inflammation.
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 surface G protein-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 mouse model of house dust mite-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 LPA2 attenuates Th2-driven allergic airway inflammation in a mouse model of asthma. Targeting LPA receptor signaling holds therapeutic promise in allergic asthma.
authors.affiliation: 1 Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Knowlden
authors.affiliation: 2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, Rochester, New York.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Hillman
authors.affiliation: 2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, Rochester, New York.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Chapman
authors.affiliation: 3 Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee; and.|4 Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: Renukadevi
authors.initials: R
authors.lastname: Patil
authors.affiliation: 4 Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: Duane D
authors.initials: DD
authors.lastname: Miller
authors.affiliation: 3 Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee; and.
authors.forename: Gabor
authors.initials: G
authors.lastname: Tigyi
authors.affiliation: 1 Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York.|2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, Rochester, New York.
authors.forename: Steve N
authors.initials: SN
authors.lastname: Georas
mesh_terms: D000485:Allergens; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008807:Mice, Inbred BALB C; D053644:Naphthalimides / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D049368:Receptors, Lysophosphatidic Acid / Q000819:agonists* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D000099189:Lysophospholipase D
chemical_list: D000485:Allergens; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D053644:Naphthalimides; D010727:Phosphoric Diester Hydrolases; D049368:Receptors, Lysophosphatidic Acid; D013449:Sulfonamides; D000099189:Lysophospholipase D; C000602829:2-(4-(1,3-dioxo-1H,3H-benzoisoquinolin-2-yl)butylsulfamoyl)benzoic acid
keywords: asthma; house dust mite; lysophosphatidic acid; periostin