The Research Of TLR-4Expression In Airway Innammation And Mucus Hypersecretion With Chronic Obstructive Pulmonary Disease

Objective To test the expression of TLR-4in patients with chronic obstructive pulmonary disease, and to explore the role of TLR4in airway innammation and mucus hypersecretion of COPD pathogenesis.Methods Specimens were collected from male lung carcinoma patients, according to their lung function, they were divided into2groups: Non-COPD group and COPD stable group, with20patients in each group. All lung specimens was observed by HE and AB-PAS staining. The expression of TLR-4, HBD-2, IL-8, MUC5AC were observed by immunohistochemical staining.Results①Inflammation cells of airway walls increased in COPD group the degree of airway inflammation were higher in COPD group (2.67±0.26) than Non-COPD group (1.15±0.34)(P<0.05). the percentage of Goblet cells were higher in COPD group (27.83±6.72) than Non-COPD group (12.67±4.12).MUC5AC mainly express in the goblet cells of airway epithelial, the expression of MUC5AC were higher in COPD group (24.16±3.63) than Non-COPD group(16.12±4.41)(P<0.05).②The expression of TLR-4、IL-8and HBD-2in COPD group (IOD=1110.12±302.61,1480.23±292.51,1496.41±346.86) were higher than Non-COPD group (IOD=724.21±242.13,864.31±121.53,654.46±215.16)(P<0.05). TLR-4major express in pulmonary macrophage, neutrophils, airway epithelial cells, vascular endothelial cells, and smooth muscle cells. IL-8express in neutrophils, macrophages of airway walls, alveolar interval, hemal walls;HBD-2express in epithelial cells of airway walls.③The degree of airway inflammation, the percentage of goblet cells and the positive rate of MUC5AC were higher in smokers (2.67±0.28,64.12±1.13,32.43±1.21) than non-smokers (1.02±0.14,30.12±1.13,12.98±1.76)(P<0.05).④TLR-4were positively correlated with airway neutrophils percentage, IL-8and HBD-2(r=0.66,0.92,0.72, P<0.05). TLR-4was positively correlated with MUC5AC(r=0.74, P<0.05). IL-8was positively correlated with MUC5AC(r=0.82, P<0.05). IL-8was positively correlated with airway neutrophils percentage (r=0.94, P<0.05). The degree of airway inflammation, the percentage of goblet cells and the positive rate of MUC5AC were positively correlated with smoking index(r=0.86、0.89、0.81, P<0.05).Conclusion The high expression of TLR-4induced the increased of IL-8and HBD-2in COPD, involved airways innammation in COPD pathogenesis. The increase of HBD may further amplify TLR-4mediated inflammation responses, because HBD act as endogenous ligands for TLR4. The high expression of TLR-4induced the increased of MUC5AC in the airways may be one of mechanism involved mucus hypersecretion in COPD, but not the direct effect.