Chemokine receptor CXCR3 is important for lung tissue damage and airway remodeling induced by short-term exposure to cigarette smoking in mice  

作　　者：Li NIE Zhen-jia LIU Wei-xun ZHOU Ruo-lan XIANG Yu XIAO Bao LU Bao-sen PANG Jin-ming GAO 

机构地区：[1]Department of Respiratory Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China [2]Department of Respiratory Diseases, West China Hospital, Sichuan University, Chengdu 610041, China [3]Department of Pathology, Peking Union Medical Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China [4]Department of Physiology and Pathophysiology, Peking University Health Sciences Center, Beijing 100191, China [5]Ina Sue Perlmutter Laboratory, Division of Pulmonary, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA [6]Institute of Respiratory Diseases, Chaoyang Hospital, Capital Medical University, Beijing 100020, China

出　　处：《Acta Pharmacologica Sinica》2010年第4期436-442,共7页中国药理学报（英文版）

摘　　要：Aim： To investigate the role of chemokine receptor CXCR 3 in cigarette smoking （CS）-induced pulmonary damage. Methods： CXCR3 knockout （CXCR3-/-） mice were used. Differences in airspace enlargement, mRNA expression of matrix metalloproteinases （MMPs）, transforming growth factor （TGF） β1, CXCL 10 in lung homogenates, and CXCL10 content in bronchoalveolar lavage （BAL） fluids and homogenates were compared between CXCR3-/- mice and wild-type （WT） mice three days after three-day CS exposures. Results： The linear intercept was significantly less in CXCR3-/- mice than in WT mice （30.1±0.9 μm vs 40.3±2.4 μm, P〈0.01）. Morphologically, collagen was deposited less around airways and vessels in CXCR3-/- mice. The lung hydroxyproline content was significantly lower in CXCR3-/- mice than in WT mice （6.0±1.0 μg/mL vs 12.0±1.6 μg/mL, P〈0.05）. Profoundly lower mRNA expression of MMP2, MMP12, TGFβ1, and CXCL10 was seen in lung homogenates from CXCR3-/- mice. CXCL10 concentrations in BAL fluid and lung homogenates were significantly lower in CXCR3-/- mice than in WT mice （BAL fluid： 19.3±1.4 pg/mL vs 24.8±1.6 pg/mL, P〈0.05; lung homogenates： 76.6±7.0 pg/mL vs 119.5±15.9 pg/mL, P〈0.05）. Conclusion： CXCR3 is important in mediating lung tissue damage and airway remodeling following a short-term CS insult, possibly through up-regulation of CXCL10 and inducement of mRNA expression of MMPs. Targeting CXCR3 may be helpful for prevention of CS-induced pulmonary pathology.Aim： To investigate the role of chemokine receptor CXCR 3 in cigarette smoking （CS）-induced pulmonary damage. Methods： CXCR3 knockout （CXCR3-/-） mice were used. Differences in airspace enlargement, mRNA expression of matrix metalloproteinases （MMPs）, transforming growth factor （TGF） β1, CXCL 10 in lung homogenates, and CXCL10 content in bronchoalveolar lavage （BAL） fluids and homogenates were compared between CXCR3-/- mice and wild-type （WT） mice three days after three-day CS exposures. Results： The linear intercept was significantly less in CXCR3-/- mice than in WT mice （30.1±0.9 μm vs 40.3±2.4 μm, P〈0.01）. Morphologically, collagen was deposited less around airways and vessels in CXCR3-/- mice. The lung hydroxyproline content was significantly lower in CXCR3-/- mice than in WT mice （6.0±1.0 μg/mL vs 12.0±1.6 μg/mL, P〈0.05）. Profoundly lower mRNA expression of MMP2, MMP12, TGFβ1, and CXCL10 was seen in lung homogenates from CXCR3-/- mice. CXCL10 concentrations in BAL fluid and lung homogenates were significantly lower in CXCR3-/- mice than in WT mice （BAL fluid： 19.3±1.4 pg/mL vs 24.8±1.6 pg/mL, P〈0.05; lung homogenates： 76.6±7.0 pg/mL vs 119.5±15.9 pg/mL, P〈0.05）. Conclusion： CXCR3 is important in mediating lung tissue damage and airway remodeling following a short-term CS insult, possibly through up-regulation of CXCL10 and inducement of mRNA expression of MMPs. Targeting CXCR3 may be helpful for prevention of CS-induced pulmonary pathology.

关 键 词：CXCR3 CXCL10 cigarette smoking tissue damage airway remodeling 

分 类 号：Q987[生物学—遗传学] S826.1[生物学—人类学]