Novel Inhibitory Effect of a Lysophosphatidic Acid 2 Agonist on Allergen-Driven Airway Inflammation.

Autor:	Knowlden SA; 1 Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York., Hillman SE; 2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, Rochester, New York., Chapman TJ; 2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, Rochester, New York., Patil R; 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., Miller DD; 4 Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee., Tigyi G; 3 Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee; and., Georas SN; 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.
Jazyk:	angličtina
Zdroj:	American journal of respiratory cell and molecular biology [Am J Respir Cell Mol Biol] 2016 Mar; Vol. 54 (3), pp. 402-9.
DOI:	10.1165/rcmb.2015-0124OC
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu