title: Chemokine receptor CXCR3 is important for lung tissue damage and airway remodeling induced by short-term exposure to cigarette smoking in mice.
abstract: OBJECTIVE
  To investigate the role of chemokine receptor CXCR3 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) beta1, CXCL10 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 microm vs 40.3+/-2.4 microm, 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 microg/mL vs 12.0+/-1.6 microg/mL, P<0.05). Profoundly lower mRNA expression of MMP2, MMP12, TGF beta 1, 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Respiratory Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
authors.forename: Li
authors.initials: L
authors.lastname: Nie
authors.forename: Zhen-jia
authors.initials: ZJ
authors.lastname: Liu
authors.forename: Wei-xun
authors.initials: WX
authors.lastname: Zhou
authors.forename: Ruo-lan
authors.initials: RL
authors.lastname: Xiang
authors.forename: Yu
authors.initials: Y
authors.lastname: Xiao
authors.forename: Bao
authors.initials: B
authors.lastname: Lu
authors.forename: Bao-sen
authors.initials: BS
authors.lastname: Pang
authors.forename: Jin-ming
authors.initials: JM
authors.lastname: Gao
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D054367:Receptors, CXCR3 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012907:Smoking / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D054357:Chemokine CXCL10; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases