Acute pulmonary inflammation is inhibited in CXCR3 knockout mice after short-term cigarette smoke exposure.
OBJECTIVE
CXCR3, via binding its specific ligand CXCL10, plays an important role in cigarette smoke (CS)-induced pulmonary inflammation. CXCR3 is preferentially expressed in activated T cells (chiefly CD8+ T cells). The purpose of this study was to investigate the role of CXCR3 in CS-induced pulmonary injury using CXCR3 gene-deficient (CXCR3-/-) mice.


METHODS
Differences in the infiltration of inflammatory cells and CD8+ T cells and the expression of inflammatory mediators and chemokines in the bronchoalveolar lavage fluid and lungs at the mRNA and protein levels were compared between CXCR3-/- mice and wild-type (WT) mice at 2 h after 3 d of CS exposure.


RESULTS
Compared with their WT counterparts, the CXCR3-/- mice showed alleviated inflammation, as evidenced by fewer inflammatory cells, particularly cytotoxic CD8+ T cells, in bronchoalveolar lavage fluid and lung tissues. At both the mRNA and protein levels, there were significantly lower levels of inflammatory and chemotactic cytokines, including TNF-alpha, interleukin-8, interferon-gamma, transforming growth factor-beta1, and CXCL10 in the CXCR3-/- mice.


CONCLUSIONS
Our data show that CXCR3 is important in recruiting inflammatory cells (particularly CD8+ T cells) into the airways and lungs, as well as initiating inflammatory and fibrotic cytokines release at 2 h following a short-term CS insult. CXCR3 could be a novel target for the treatment of pulmonary inflammation induced by CS.
Nie
Li
L
Department of Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, China.
Xiang
Ruo-lan
RL
Liu
Yong
Y
Zhou
Wei-xun
WX
Jiang
Lei
L
Lu
Bao
B
Pang
Bao-sen
BS
Cheng
De-yun
DY
Gao
Jin-Ming
JM
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011014:Pneumonia / Q000276:immunology*; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism*; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking; D014026:Nicotiana / Q000009:adverse effects*
D054357:Chemokine CXCL10; D018925:Chemokines; C515188:Cxcr3 protein, mouse; D016207:Cytokines; D054367:Receptors, CXCR3; D012906:Smoke