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

• 来源期刊: 中国药理学报(英文版)
• 关键词: CXCR3 CD8 CXCL10 cigarette smoke
• 年，卷（期）: 2008,（12）
• 页码范围: 1432-1439
• 页数: 8页
• 语种: 英文
• DOI: 10.1111/j.1745-7254.2008.00899.x

摘要

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 pur-pose of this study was to investigate the role of CXCR3 in CS-induced pul-monary 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 bronchoalveo-lar 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.