Roles of CCR2b and CCR1 antagonist RS504393 in LPS-induced acute lung injury
10.3760/cma.j.issn.1671-0282.2009.12.013
- VernacularTitle:CCR2b和CCR1拮抗剂RS504393对LPS诱导小鼠急性肺损伤的保护作用
- Author:
Dong YANG
;
Chunxue BAI
;
Xiangdong WANG
;
Lin TONG
;
Yaoli WANG
- Publication Type:Journal Article
- Keywords:
CC chemokine receptor;
Acute lung injury;
Iipopolysaccharide;
Plasminogen activator inhibitor-1;
Monocyte chemoattractant protein-2
- From:
Chinese Journal of Emergency Medicine
2009;18(12):1278-1282
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the potential effects of RS504393, CC chemokine receptor (CCR) 2b and CCR1 antagonist, on LPS-induced acute lung injury (ALI) and to investigate the underlying mechanisms. Method A549 cell line was stimulated with LPS (10 μg/mL) and then treated with RS504393 (10 μg/mL) for 6 hours. ALI model was established with intranasal administration of LPS (5 mg/kg) in C57BL/6J mice. RS504393 (5 mg/kg) was administered 30 min before LPS dripped nasally. IL-8, IL-1β, plasminogen activator inhibitor (PAI)-l,monocyte chemoattractant protein (MCP)-2,and the expressions of CCR1 and CCR2b were studied by using Realtime-RT-PCR, ELISA and cyto-flowmetry. Results In A549 cell line treated with RS504393,the expressions of CCR1, CCR2b and IL-8 were significantly inhibited after LPS stimulation. In rats with LPS-induced ALI, treatment with RS504393 significantly protected mice against lung injury by attenuating influx of leukocytes and protein into bronchoalveolar space and by lessening pathological changes of lung. Treatment with RS504393 down-regulated IL-1β and PAI-1 expressions in bronchoal veolar lavage fluid (BALF) and lungs at mRNA and protein levels along with up-regulation MCP-2 expression compared to rats of vehicle-treated groups. Conclusions CCR2b and CCR1 play pivotal roles in the development of ALl,and RS504393 as a antagonist can halt the development of ALI.
