title: Characteristics of Allergic Pulmonary Inflammation in CXCR3Knockout Mice Sensitized and Challenged with House Dust Mite Protein.
abstract: Chemokine C-X-C motif receptor 3 (CXCR3) is a chemokine receptor that is mainly expressed by activated T lymphocytes. T cells play important roles in allergic pulmonary inflammation, which is a hallmark of asthma and elicits the localized accumulation of activated T cells in the lung. In China, a marked increase in the incidence rate of chronic allergic pulmonary inflammation has made it a major public health threat. In the present study, we investigated the role of CXCR3 and its ligands in airway inflammation induced by house dust mite protein (HDMP) in a CXCR3 knockout (CXCR3KO) asthma mouse model. Pathological manifestations in the lung, cell counts and bronchoalveolar lavage fluid (BALF) classifications were studied using hematoxylin and eosin (H&E) staining. The levels of IL-4 and IFN-γ in the BALF and splenocyte supernatants were measured using ELISA. CD4+ and CD8+ T cells in the lung and spleen were analyzed by flow cytometry. RT-PCR was applied to measure the mRNA transcript levels of monokines induced by IFN-γ(CXCL9) and IFN-γ inducible protein 10(CXCL10). The total cell counts, eosinophil counts, and IL-4 levels in the BALF and cultured splenocyte supernatants were significantly increased, while the levels of IFN-γ were reduced in the HDMP groups(P<0.01). Changes in the total cell counts, eosinophil counts, and lymphocyte counts, as well as the total protein levels in the BALF, the levels of IL-4 in splenocyte supernatants, and the pathological manifestations in the lung, were all greater in CXCR3KO mice than in C57BL/6 wild-type mice. Furthermore, the expression levels of CXCL9 and CXCL10 mRNA transcripts in the lungs of CXCR3KO mice were lower than those in C57BL/6 wild-type mice (P<0.05). CXCR3 and its ligands (i.e., CXCL9 and CXCL10) may play anti-inflammatory roles in this animal model. Promoting the expression of CXCR3 and its ligands may represent a novel therapeutic approach for preventing and curing asthma.
authors.affiliation: Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Zhongjuan
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Respiratory Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Huaxia
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Respiratory Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Respiratory Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000818:Animals; D060829:Arthropod Proteins / Q000276:immunology*; D001249:Asthma / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D054370:Chemokine CXCL9 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039981:Pyroglyphidae / Q000378:metabolism*; D054367:Receptors, CXCR3 / Q000172:deficiency / Q000235:genetics*; D013154:Spleen / Q000166:cytology / Q000378:metabolism / Q000473:pathology
chemical_list: D060829:Arthropod Proteins; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D054367:Receptors, CXCR3; D015847:Interleukin-4; D007371:Interferon-gamma