Role of lysophosphatidic acid receptor LPA<sub>2 </sub>in the development of allergic airway inflammation in a murine model of asthma

<p>Abstract</p> <p>Background</p> <p>Lysophosphatidic acid (LPA) plays a critical role in airway inflammation through G protein-coupled LPA receptors (LPA<sub>1-3</sub>). We have demonstrated that LPA induced cytokine and lipid mediator release in human bron...

Full description

Bibliographic Details
Main Authors: Chun Jerold, Evgeny Berdyshev, Pendyala Srikanth, He Donghong, Tong Jiankun, Zhao Yutong, Sperling Anne I, Natarajan Viswanathan
Format: Article
Language:English
Published: BMC 2009-11-01
Series:Respiratory Research
Online Access:http://respiratory-research.com/content/10/1/114
_version_ 1818120374559178752
author Chun Jerold
Evgeny Berdyshev
Pendyala Srikanth
He Donghong
Tong Jiankun
Zhao Yutong
Sperling Anne I
Natarajan Viswanathan
author_facet Chun Jerold
Evgeny Berdyshev
Pendyala Srikanth
He Donghong
Tong Jiankun
Zhao Yutong
Sperling Anne I
Natarajan Viswanathan
author_sort Chun Jerold
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Lysophosphatidic acid (LPA) plays a critical role in airway inflammation through G protein-coupled LPA receptors (LPA<sub>1-3</sub>). 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.</p> <p>Methods</p> <p/> <p>Wild type, LPA<sub>1 </sub>heterozygous knockout mice (LPA<sub>1</sub><sup>+/-</sup>), and LPA<sub>2 </sub>heterozygous knockout mice (LPA<sub>2</sub><sup>+/-</sup>) were sensitized with inactivated <it>Schistosoma mansoni </it>eggs and local antigenic challenge with <it>Schistosoma mansoni </it>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.</p> <p>Results</p> <p>BAL fluids from <it>Schistosoma mansoni </it>egg-sensitized and challenged wild type mice (4 days of challenge) showed increase of LPA level (~2.8 fold), compared to control mice. LPA<sub>2</sub><sup>+/- </sup>mice, but not LPA<sub>1</sub><sup>+/- </sup>mice, exposed to <it>Schistosoma mansoni </it>egg revealed significantly reduced cell numbers and eosinophils in BAL fluids, compared to challenged wild type mice. Both LPA<sub>2</sub><sup>+/- </sup>and LPA<sub>1</sub><sup>+/- </sup>mice showed decreases in bronchial goblet cells. LPA<sub>2</sub><sup>+/- </sup>mice, but not LPA<sub>1</sub><sup>+/- </sup>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 LPA<sub>2</sub><sup>+/- </sup>mice. These results suggest that LPA and LPA receptors are involved in <it>Schistosoma mansoni </it>egg-mediated inflammation and further studies are proposed to understand the role of LPA and LPA receptors in the inflammatory process.</p>
first_indexed 2024-12-11T05:25:05Z
format Article
id doaj.art-16a028a020d24c57aa1434adde2bec0f
institution Directory Open Access Journal
issn 1465-9921
language English
last_indexed 2024-12-11T05:25:05Z
publishDate 2009-11-01
publisher BMC
record_format Article
series Respiratory Research
spelling doaj.art-16a028a020d24c57aa1434adde2bec0f2022-12-22T01:19:35ZengBMCRespiratory Research1465-99212009-11-0110111410.1186/1465-9921-10-114Role of lysophosphatidic acid receptor LPA<sub>2 </sub>in the development of allergic airway inflammation in a murine model of asthmaChun JeroldEvgeny BerdyshevPendyala SrikanthHe DonghongTong JiankunZhao YutongSperling Anne INatarajan Viswanathan<p>Abstract</p> <p>Background</p> <p>Lysophosphatidic acid (LPA) plays a critical role in airway inflammation through G protein-coupled LPA receptors (LPA<sub>1-3</sub>). 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.</p> <p>Methods</p> <p/> <p>Wild type, LPA<sub>1 </sub>heterozygous knockout mice (LPA<sub>1</sub><sup>+/-</sup>), and LPA<sub>2 </sub>heterozygous knockout mice (LPA<sub>2</sub><sup>+/-</sup>) were sensitized with inactivated <it>Schistosoma mansoni </it>eggs and local antigenic challenge with <it>Schistosoma mansoni </it>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.</p> <p>Results</p> <p>BAL fluids from <it>Schistosoma mansoni </it>egg-sensitized and challenged wild type mice (4 days of challenge) showed increase of LPA level (~2.8 fold), compared to control mice. LPA<sub>2</sub><sup>+/- </sup>mice, but not LPA<sub>1</sub><sup>+/- </sup>mice, exposed to <it>Schistosoma mansoni </it>egg revealed significantly reduced cell numbers and eosinophils in BAL fluids, compared to challenged wild type mice. Both LPA<sub>2</sub><sup>+/- </sup>and LPA<sub>1</sub><sup>+/- </sup>mice showed decreases in bronchial goblet cells. LPA<sub>2</sub><sup>+/- </sup>mice, but not LPA<sub>1</sub><sup>+/- </sup>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 LPA<sub>2</sub><sup>+/- </sup>mice. These results suggest that LPA and LPA receptors are involved in <it>Schistosoma mansoni </it>egg-mediated inflammation and further studies are proposed to understand the role of LPA and LPA receptors in the inflammatory process.</p>http://respiratory-research.com/content/10/1/114
spellingShingle Chun Jerold
Evgeny Berdyshev
Pendyala Srikanth
He Donghong
Tong Jiankun
Zhao Yutong
Sperling Anne I
Natarajan Viswanathan
Role of lysophosphatidic acid receptor LPA<sub>2 </sub>in the development of allergic airway inflammation in a murine model of asthma
Respiratory Research
title Role of lysophosphatidic acid receptor LPA<sub>2 </sub>in the development of allergic airway inflammation in a murine model of asthma
title_full Role of lysophosphatidic acid receptor LPA<sub>2 </sub>in the development of allergic airway inflammation in a murine model of asthma
title_fullStr Role of lysophosphatidic acid receptor LPA<sub>2 </sub>in the development of allergic airway inflammation in a murine model of asthma
title_full_unstemmed Role of lysophosphatidic acid receptor LPA<sub>2 </sub>in the development of allergic airway inflammation in a murine model of asthma
title_short Role of lysophosphatidic acid receptor LPA<sub>2 </sub>in the development of allergic airway inflammation in a murine model of asthma
title_sort role of lysophosphatidic acid receptor lpa sub 2 sub in the development of allergic airway inflammation in a murine model of asthma
url http://respiratory-research.com/content/10/1/114
work_keys_str_mv AT chunjerold roleoflysophosphatidicacidreceptorlpasub2subinthedevelopmentofallergicairwayinflammationinamurinemodelofasthma
AT evgenyberdyshev roleoflysophosphatidicacidreceptorlpasub2subinthedevelopmentofallergicairwayinflammationinamurinemodelofasthma
AT pendyalasrikanth roleoflysophosphatidicacidreceptorlpasub2subinthedevelopmentofallergicairwayinflammationinamurinemodelofasthma
AT hedonghong roleoflysophosphatidicacidreceptorlpasub2subinthedevelopmentofallergicairwayinflammationinamurinemodelofasthma
AT tongjiankun roleoflysophosphatidicacidreceptorlpasub2subinthedevelopmentofallergicairwayinflammationinamurinemodelofasthma
AT zhaoyutong roleoflysophosphatidicacidreceptorlpasub2subinthedevelopmentofallergicairwayinflammationinamurinemodelofasthma
AT sperlingannei roleoflysophosphatidicacidreceptorlpasub2subinthedevelopmentofallergicairwayinflammationinamurinemodelofasthma
AT natarajanviswanathan roleoflysophosphatidicacidreceptorlpasub2subinthedevelopmentofallergicairwayinflammationinamurinemodelofasthma