Prostaglandin E2 Exerts Homeostatic Regulation of Pulmonary Vascular Remodeling in Allergic Airway Inflammation

被引:59
作者
Lundequist, Anders [1 ,2 ]
Nallamshetty, Samridhi N. [1 ,2 ]
Xing, Wei [1 ,2 ]
Feng, Chunli [1 ]
Laidlaw, Tanya M. [1 ,2 ,3 ]
Uematsu, Satoshi [4 ]
Akira, Shizuo [4 ]
Boyce, Joshua A. [1 ,2 ,3 ]
机构
[1] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA
[4] Osaka Univ, Dept Host Def, Res Inst Microbial Dis, Osaka, Japan
基金
美国国家卫生研究院;
关键词
DENDRITIC CELLS; INDUCED ARTHRITIS; IMMUNE-RESPONSE; INHALED PGE(2); E SYNTHASE-1; ASTHMA; RECEPTORS; MICE; LUNG; ACTIVATION;
D O I
10.4049/jimmunol.0902835
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Nonselective inhibition of PG synthesis augments inflammation in mouse models of airway disease, but the roles of individual PGs are not completely clarified. To investigate the role of PGE(2) in a mouse model of airway inflammation induced by a natural allergen, we used mice lacking the critical terminal synthetic enzyme, microsomal PGE(2) synthase (mPGES)-1. Mice lacking mPGES-1 (ptges(-/-) mice) and wild-type C57BL/6 controls were challenged intranasally with low doses of an extract derived from the house dust mite Dernialophagoides farinae (Der f). The levels of PGE(2) in the bronchoalveolar lavage fluids of Der f-treated ptges(-/-) mice were similar to 80% lower than the levels in wild-type controls. Der f-induced bronchovascular eosinophilia was modestly enhanced in the ptges(-/-) mice. Both Der f-treated strains showed similar increases in serum IgE and IgGI, as well as comparable levels of Th1, Th2, and Th17 cytokine production by Der f-stimulated spleen cells. These findings indicated that mPGES-1-derived PGE(2) was not required for allergen sensitization or development of effector T cell responses. Unexpectedly, the numbers of vascular smooth muscle cells and the thickness of intrapulmonary vessels were both markedly increased in the Der f-treated ptges(-/-) mice. These vascular changes were suppressed by the administration of the stable PGE(2) analog 16, 16-dimethyl PGE(2), or of selective agonists of the E-prostanoid (EP) 1, EP2, and EP3 receptors, respectively, for PGE(2). Thus, mPGES-1 and its product, PGE(2), protect the pulmonary vasculature from remodeling during allergen-induced pulmonary inflammation, and these effects may be mediated by more than one EP receptor. The Journal of Immunology, 2010, 184: 433-441.
引用
收藏
页码:433 / 441
页数:9
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