Acta Pharmacologica Sinica 2008 December; 29 (12): 1432-1439; doi: 10.1111/j.1745-7254.2008.00899.x

Acta Pharmacologica Sinica 2008 December; 29 (12): 1432-1439; doi: 10.1111/j.1745-7254.2008.00899.x

Original Article

Acute pulmonary inflammation is inhibited in CXCR3 knockout mice after short-term cigarette smoke exposure¹

Li NIE^2,3,8, Ruo-lan XIANG^5,8, Yong LIU^3,8, Wei-xun ZHOU⁴, Lei JIANG³, Bao LU⁶, Bao-sen PANG⁷, De-yun CHENG², Jin-ming GAO^3,9

²Department of Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610041, China; Departments of ³Respiratory Disease and ⁴Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; ⁵Department of Pathophysiology, Peking University Health Sciences Center, Beijing 100088, China; ⁶Ina Sue Perlmutter Laboratory, Harvard Medical School, Boston, Massachusetts 02115, USA; ⁷Respiratory Institute, Capital Medical University, Beijing 100020, China

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.

Keywords: CXCR3; CD8; CXCL10; cigarette smoke

¹This 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).

⁸These authors contributed equally to this work.
⁹Correspondence to Dr Jin-ming GAO.
Phn 86-10-6529-5035.
Fax 86-10-6512-4875.
E-mail gaojm@pumch.cn
Received 2008-06-29 Accepted 2008-09-12

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