共 37 条
Inhibition of Pyk2 Blocks Airway Inflammation and Hyperresponsiveness in a Mouse Model of Asthma
被引:24
作者:
Duan, Yingli
[1
]
Learoyd, Jonathan
[1
]
Meliton, Angelo Y.
[1
]
Clay, Bryan S.
[1
]
Leff, Alan R.
[1
,2
,3
,4
,5
,6
]
Zhu, Xiangdong
[1
]
机构:
[1] Univ Chicago, Dept Med, Pulm & Crit Care Med Sect, Chicago, IL 60637 USA
[2] Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA
[3] Univ Chicago, Dept Neurobiol, Chicago, IL 60637 USA
[4] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA
[5] Univ Chicago, Dept Comm Clin Pharmacol, Chicago, IL 60637 USA
[6] Univ Chicago, Dept Cell Physiol & Mol Med, Div Biol Sci, Chicago, IL 60637 USA
关键词:
eosinophils;
Pyk2;
inflammation;
lung;
RICH TYROSINE KINASE-2;
PROTEIN TRANSDUCTION;
MURINE MODEL;
EOSINOPHILS;
CELLS;
INTERLEUKIN-5;
MIGRATION;
MICE;
ACTIVATION;
EOTAXIN;
D O I:
10.1165/rcmb.2008-0469OC
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
The objective of this investigation was to determine the role of Pyk2, an intracellular nonreceptor protein tyrosine kinase for postadhesive inflammatory cell migration, on airway inflammation and hyperresponsiveness in immune-sensitized mice. Blockade of Pyk2 was effected by intraperitoneal administration of dominant-negative C-terminal Pyk2 fused to a TAT protein transduction domain (TAT-Pyk2-CT). Ovalbumin challenge elicited infiltration of both eosinophils and lymphocytes into airways, increased mucus-containing epithelial cells, and caused increased airway hyperresponsiveness to methacholine in immune-sensitized mice. Pretreatment with 10 mg/kg TAT-Pyk2-CT intraperitoneally blocked all of these effects and further decreased secretion of Th2 cytokine IL-4, IL-5, and IL-13 into the bronchoalveolar lavage fluid. Intranasal administration of IL-5 caused eosinophil migration into the airway lumen, which was attenuated by systemic pretreatment with TAT-Pyk2-CT. In each paradigm, treatment with control protein TAT-GFP had no blocking effect. We conclude that Pyk2, which is essential for inflammatory cell migration in vitro, regulates airway inflammation, Th2 cytokine secretion, and airway hyperresponsiveness in the ovalbumin-sensitized mice during antigen challenge in vivo.
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页码:491 / 497
页数:7
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