CXC chemokine receptor 3 modulates bleomycin-induced pulmonary injury via involving inflammatory process.
OBJECTIVE
To investigate the role of CXC chemokine receptor 3 (CXCR3) in bleomycin-induced lung injury by using CXCR3 gene deficient mice.


METHODS
Sex-, age-, and weight-matched C57BL/6 CXCR3 gene knockout mice and C57BL/6 wide type mice were challenged by injection of bleomycin via trachea. Lung tissue was stained with HE method. Airway resistance was measured. Bronchoalveolar lavage (BAL) was performed using phosphate buffered saline twice, cell number and differentials were counted by Diff-Quick staining. Interleukin (IL)4, IL-5, IL-12p40, and interfon-y in BAL fluid and lung homogenate were measured by enzyme-linked immunosorbent assay. Unpaired t test was explored to compare the difference between two groups.


RESULTS
On day 7 after bleomycin injection via trachea, CXCR3 knockout mice were protected from bleomycin-induced lung injury as evidenced by fewer accumulation of inflammatory cells in the airway and lung interstitium compared with their wild type littermates (P < 0.05). Airway resistance was also lower in CXCR3 knockout mice compared with wild type mice (P < 0.01). Significantly lower level of inflammatory cytokines release, including the altered production of IL-4 and IL-5 both in BAL fluid and lung tissue was seen in CXCR3 knockout mice than in wild type mice (both P<0.05).


CONCLUSIONS
CXCR3 signaling promotes inflammatory cells recruiting and initiates inflammatory cytokines cascade following endotracheal bleomycin administration, indicating that CXCR3 might be a therapeutic target for pulmonary injury.
Gao
Jin-ming
JM
Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730. gaojm@pumch.cn
Lu
Bao
B
Guo
Zi-jian
ZJ
D000403:Airway Resistance; D000818:Animals; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002452:Cell Count; D016207:Cytokines / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics / Q000502:physiology*
C515188:Cxcr3 protein, mouse; D016207:Cytokines; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D001761:Bleomycin; D007371:Interferon-gamma