期刊
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
卷 45, 期 4, 页码 851-857出版社
AMER THORACIC SOC
DOI: 10.1165/rcmb.2010-0455OC
关键词
LAR; EAR; established asthma; BLT1 antagonist
资金
- NIH [HL-36577, HL-61005, AI-77609]
- EPA [R825702]
- Ministry of Education, Science and Culture of Japan
- NOVARTIS Foundation for the Promotion of Science
- Novartis
- Takeda Science Foundation
- AstraZeneca
- GlaxoSmith Kline
- Merck
- Boehringer Ingelheim
- Kalypsys
- Chemizon
- Grants-in-Aid for Scientific Research [22591092] Funding Source: KAKEN
Most of the studies investigating the effectiveness of blocking the leukotriene B4 (LTB4) receptor 1 (BLT1) have been performed in models of primary or acute allergen challenge. The role of the LTB4-BLT1 pathway in secondary challenge models, where airway hyperresponsiveness (AHR) and airway inflammation have been established, has not been defined. We investigated the effects of blocking BLT1 on early-and late-phase development of AHR and airway inflammation in previously sensitized and challenged mice. Female BALB/c mice were sensitized (Days 1 and 14) and challenged (primary, Days 28-30) with ovalbumin. On Day 72, mice were challenged (secondary) with a single OVA aerosol, and the early and late phases of AHR and inflammation were determined. Specific blockade of BLT1 was attained by oral administration of a BLT1 antagonist on Days 70 through 72. Administration of the antagonist inhibited the secondary ovalbumin challenge-induced alterations in airway responses during the late phase but not during the early phase, as demonstrated by decreases in AHR and in bronchoalveolar lavage neutrophilia and eosinophilia 6 and 48 hours after secondary challenge. The latter was associated with decreased levels of KC protein, macrophage inflammatory protein 2, and IL-17 in the airways. These data identify the importance of the LTB4-BLT1 pathway in the development of late-phase, allergen-induced airway responsiveness after secondary airway challenge in mice with established airway disease.
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