Role of lysophosphatidic acid receptor LPA2 in the development of allergic airway inflammation in a murine model of asthma.
BACKGROUND
Lysophosphatidic acid (LPA) plays a critical role in airway inflammation through G protein-coupled LPA receptors (LPA1-3). We have demonstrated that LPA induced cytokine and lipid mediator release in human bronchial epithelial cells. Here we provide evidence for the role of LPA and LPA receptors in Th2-dominant airway inflammation.


METHODS
Wild type, LPA1 heterozygous knockout mice (LPA1+/-), and LPA2 heterozygous knockout mice (LPA2+/-) were sensitized with inactivated Schistosoma mansoni eggs and local antigenic challenge with Schistosoma mansoni soluble egg Ag (SEA) in the lungs. Bronchoalveolar larvage (BAL) fluids and lung tissues were collected for analysis of inflammatory responses. Further, tracheal epithelial cells were isolated and challenged with LPA.


RESULTS
BAL fluids from Schistosoma mansoni egg-sensitized and challenged wild type mice (4 days of challenge) showed increase of LPA level (approximately 2.8 fold), compared to control mice. LPA2+/- mice, but not LPA1+/- mice, exposed to Schistosoma mansoni egg revealed significantly reduced cell numbers and eosinophils in BAL fluids, compared to challenged wild type mice. Both LPA2+/- and LPA1+/- mice showed decreases in bronchial goblet cells. LPA2+/- mice, but not LPA1+/- mice showed the decreases in prostaglandin E2 (PGE2) and LPA levels in BAL fluids after SEA challenge. The PGE2 production by LPA was reduced in isolated tracheal epithelial cells from LPA2+/- mice. These results suggest that LPA and LPA receptors are involved in Schistosoma mansoni egg-mediated inflammation and further studies are proposed to understand the role of LPA and LPA receptors in the inflammatory process.
Zhao
Yutong
Y
Department of Medicine, The University of Chicago, Chicago, Illinois, USA. yzhao@medicine.bsd.uchicago.edu
Tong
Jiankun
J
He
Donghong
D
Pendyala
Srikanth
S
Evgeny
Berdyshev
B
Chun
Jerold
J
Sperling
Anne I
AI
Natarajan
Viswanathan
V
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004527:Egg Proteins / Q000276:immunology; D020397:Goblet Cells / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism*; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D049368:Receptors, Lysophosphatidic Acid / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000276:immunology; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D000953:Antigens, Protozoan; D016207:Cytokines; D004527:Egg Proteins; D018836:Inflammation Mediators; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone; C032881:lysophosphatidic acid