Abstract
Aim:
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-α, interleukin-8, interferon-γ, transforming growth factor-β1, and CXCL10 in the CXCR3−/− mice.
Conclusion:
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.
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This work was supported by grants from the National Natural Science Foundation of China (No 30470767), Beijing Natural Science Foundation (No 7072063), and the Education Ministry of China Grant (NCET 06-0156).
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Nie, L., Xiang, Rl., Liu, Y. et al. Acute pulmonary inflammation is inhibited in CXCR3 knockout mice after short-term cigarette smoke exposure. Acta Pharmacol Sin 29, 1432–1439 (2008). https://doi.org/10.1111/j.1745-7254.2008.00899.x
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DOI: https://doi.org/10.1111/j.1745-7254.2008.00899.x
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