title: IFN-gamma-inducible protein 10 (CXCL10) contributes to airway hyperreactivity and airway inflammation in a mouse model of asthma.
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.
authors: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors: Benjamin D
authors: BD
authors: Medoff
authors: Alain
authors: A
authors: Sauty
authors: Andrew M
authors: AM
authors: Tager
authors: James A
authors: JA
authors: Maclean
authors: R Neal
authors: RN
authors: Smith
authors: Anuja
authors: A
authors: Mathew
authors: Jennifer H
authors: JH
authors: Dufour
authors: Andrew D
authors: AD
authors: Luster
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000276:immunology; D007274:Injections, Intraperitoneal; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000494:pharmacology; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; C515203:Cxcl11 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma; D010047:Ovalbumin