Chemokine receptor CXCR3 is important for lung tissue damage and airway remodeling induced by short-term exposure to cigarette smoking in mice.
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.
Nie
Li
L
Department of Respiratory Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
Liu
Zhen-jia
ZJ
Zhou
Wei-xun
WX
Xiang
Ruo-lan
RL
Xiao
Yu
Y
Lu
Bao
B
Pang
Bao-sen
BS
Gao
Jin-ming
JM
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
D054357:Chemokine CXCL10; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases