1. IFN-gamma-inducible protein 10 (CXCL10) contributes to airway hyperreactivity and airway inflammation in a mouse model of asthma.
- Author
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Medoff BD, Sauty A, Tager AM, Maclean JA, Smith RN, Mathew A, Dufour JH, and Luster AD
- Subjects
- Animals, Asthma pathology, Bronchial Hyperreactivity metabolism, Bronchial Hyperreactivity pathology, Chemokine CXCL10, Chemokine CXCL11, Chemokine CXCL9, Chemokines, CXC biosynthesis, Chemokines, CXC genetics, Disease Models, Animal, Inflammation immunology, Injections, Intraperitoneal, Interferon-gamma pharmacology, Lung metabolism, Mice, Mice, Inbred BALB C, Mice, Knockout, Mice, Transgenic, Ovalbumin administration & dosage, Ovalbumin immunology, Up-Regulation genetics, Up-Regulation immunology, Asthma immunology, Bronchial Hyperreactivity immunology, Chemokines, CXC physiology, Intercellular Signaling Peptides and Proteins, Lung pathology
- Abstract
Allergic asthma is an inflammatory disease of the airways characterized by eosinophilic inflammation and airway hyper-reactivity. Cytokines and chemokines specific for Th2-type inflammation predominate in asthma and in animal models of this disease. The role of Th1-type inflammatory mediators in asthma remains controversial. IFN-gamma-inducible protein 10 (IP-10; CXCL10) is an IFN-gamma-inducible chemokine that preferentially attracts activated Th1 lymphocytes. IP-10 is up-regulated in the airways of asthmatics, but its function in asthma is unclear. To investigate the role of IP-10 in allergic airway disease, we examined the expression of IP-10 in a murine model of asthma and the effects of overexpression and deletion of IP-10 in this model using IP-10-transgenic and IP-10-deficient mice. Our experiments demonstrate that IP-10 is up-regulated in the lung after allergen challenge. Mice that overexpress IP-10 in the lung exhibited significantly increased airway hyperreactivity, eosinophilia, IL-4 levels, and CD8(+) lymphocyte recruitment compared with wild-type controls. In addition, there was an increase in the percentage of IL-4-secreting T lymphocytes in the lungs of IP-10-transgenic mice. In contrast, mice deficient in IP-10 demonstrated the opposite results compared with wild-type controls, with a significant reduction in these measures of Th2-type allergic airway inflammation. Our results demonstrate that IP-10, a Th1-type chemokine, is up-regulated in allergic pulmonary inflammation and that this contributes to the airway hyperreactivity and Th2-type inflammation seen in this model of asthma.
- Published
- 2002
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