Attenuation of acute lung inflammation induced by cigarette smoke in CXCR3 knockout mice. 2008

Li Nie, and Ruolan Xiang, and Weixun Zhou, and Bao Lu, and Deyun Cheng, and Jinming Gao
Department of Respiratory Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, PR China. bywaters@163.com

BACKGROUND CD8+ T cells may participate in cigarette smoke (CS) induced-lung inflammation in mice. CXCL10/IP-10 (IFNgamma-inducible protein 10) and CXCL9/Mig (monokine induced by IFN-gamma) are up-regulated in CS-induced lung injury and may attract T-cell recruitment to the lung. These chemokines together with CXCL11/ITAC (IFN-inducible T-cell alpha chemoattractant) are ligands for the chemokine receptor CXCR3 which is preferentially expressed chiefly in activated CD8+ T cells. The purpose of this investigation was to study the contribution of CXCR3 to acute lung inflammation induced by CS using CXCR3 knockout (KO) mice. METHODS Mice (n = 8 per group) were placed in a closed plastic box connected to a smoke generator and were exposed whole body to the tobacco smoke of five cigarettes four times a day for three days. Lung pathological changes, expression of inflammatory mediators in bronchoalveolar lavage (BAL) fluid and lungs at mRNA and protein levels, and lung infiltration of CD8+ T cells were compared between CXCR3-/- mice and wild type (WT) mice. RESULTS Compared with the WT littermates, CXCR3 KO mice showed less CS-induced lung inflammation as evidenced by less infiltration of inflammatory cells in airways and lung tissue, particularly fewer CD8+ T cells, lower levels of IFNgamma and CXCR3 ligands (particularly CXCL10). CONCLUSIONS Our findings show that CXCR3 is important in promoting CD8+ T cell recruitment and in initiating IFNgamma and CXCL10 release following CS exposure. CXCR3 may represent a promising therapeutic target for acute lung inflammation induced by CS.

UI MeSH Term Description Entries
D011014 Pneumonia Infection of the lung often accompanied by inflammation. Experimental Lung Inflammation,Lobar Pneumonia,Lung Inflammation,Pneumonia, Lobar,Pneumonitis,Pulmonary Inflammation,Experimental Lung Inflammations,Inflammation, Experimental Lung,Inflammation, Lung,Inflammation, Pulmonary,Inflammations, Lung,Inflammations, Pulmonary,Lobar Pneumonias,Lung Inflammation, Experimental,Lung Inflammations,Lung Inflammations, Experimental,Pneumonias,Pneumonias, Lobar,Pneumonitides,Pulmonary Inflammations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012906 Smoke Visible gaseous suspension of carbon and other particulate matter emitted from burning substances.
D014026 Nicotiana A plant genus of the family SOLANACEAE. Members contain NICOTINE and other biologically active chemicals; the dried leaves of Nicotiana tabacum are used for SMOKING. Tobacco Plant,Nicotiana tabacum,Plant, Tobacco,Plants, Tobacco,Tobacco Plants
D014028 Tobacco Smoke Pollution Contamination of the air by tobacco smoke. Air Pollution, Tobacco Smoke,Environmental Pollution, Tobacco Smoke,Passive Smoking,Smoking, Passive,Environmental Smoke Pollution, Tobacco,Environmental Tobacco Smoke Pollution,Involuntary Smoking,Second Hand Smoke,Secondhand Smoke,Secondhand Smoking,Hand Smoke, Second,Hand Smokes, Second,Involuntary Smokings,Passive Smokings,Pollution, Tobacco Smoke,Pollutions, Tobacco Smoke,Second Hand Smokes,Secondhand Smokes,Secondhand Smokings,Smoke Pollution, Tobacco,Smoke Pollutions, Tobacco,Smoke, Second Hand,Smoke, Secondhand,Smokes, Second Hand,Smokes, Secondhand,Smoking, Involuntary,Smoking, Secondhand,Smokings, Involuntary,Smokings, Passive,Smokings, Secondhand,Tobacco Smoke Pollutions
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D054367 Receptors, CXCR3 CXCR receptors that are expressed on the surface of a number of cell types, including T-LYMPHOCYTES; NK CELLS; DENDRITIC CELLS; and a subset of B-LYMPHOCYTES. The receptors are activated by CHEMOKINE CXCL9; CHEMOKINE CXCL10; and CHEMOKINE CXCL11. Antigens, CD183,CD183 Antigens,CXC Chemokine Receptor 3,CXCR3 Receptors,CMKBR3 Chemokine Receptors,CXC Chemokine Receptors 3,CXCR3 Receptor,Chemokine (C-C Motif) Receptor 3,Chemokine Receptors, CMKBR3,Receptor, CXCR3,Receptors, CMKBR3 Chemokine
D018345 Mice, Knockout Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes. Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out

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