A Regulatory Role of Chemokine Receptor CXCR3 in the Pathogenesis of Chronic Obstructive Pulmonary Disease and Emphysema

AbstractChronic obstructive pulmonary disease (COPD)/pulmonary emphysema is driven by the dysregulated airway inflammation and primarily influenced by the interaction between cigarette smoking (CS) and the individual ’s susceptibility. The inflammation in COPD involves both innate and adaptive immunity. By binding to its specific ligands, chemokine receptorCXCR3 plays an important role in regulating tissue inflammation and damage. In acute animal model challenged with either CS or pathogens,CXCR3 knockout (KO) attenuated lung inflammation and pathology. However, the role ofCXCR3 in CS-induced chronic airway inflammation and pulmonary emphysema remains unknown. In this present study, we investigated the effect ofCXCR3 in CS-induced pulmonary emphysema in an animal model, and the association betweenCXCR3 single nucleotide polymorphisms (SNPs) and COPD susceptibility in human subjects. We found that after chronic exposure to side stream CS (SSCS) for 24 weeks,CXCR3 KO mice demonstrated significant airspace enlargement expressed by mean linear intercept (Lm) compared with the wild-type (WT) mice. Consistently,CXCR3 KO mice had significantly higher BAL fluid macrophages and neutrophils, TNF α, and lung homogenate MMP-9 and MMP-12. Through genetic analysis ofCXCR3 polymorphisms in a cohort of COPD patients with Han Chinese ethnicity, oneCXCR3 SNP, rs2280964, was found to be genetically related to COPD susceptibility. Furthermore,CXCR3 SNP rs2280964 was significantly associated w...
Source: Inflammation - Category: Allergy & Immunology Source Type: research