Expressions of tumor necrosis factor-converting enzyme and ErbB3 in rats with chronic obstructive pu

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Background Chronic obstructive pulmonary disease(COPD)is associated not only with airway inflammationcharacterized by mucin hypersecretion but also with systemic inflammation.Tumor necrosis factor alpha(TNF-a)is foundto take part in systemic inflammation,and ErbB3 plays an important role in mucin hypersecretion of COPD.Since TNF-αconverting enzyme(TACE)is involved in the activation of both TNF-a and ErbB3,we established rat models of COPD toinvestigate the expressions of TACE,TNF-α and ErbB3 and to explore the correlations among TACE,TNF-α and ErbB3respectively.Methods Thirty Wistar male rats were randomly divided into COPD group(group C,n=10),saline solution parallelgroup(group P,n=8),and normal control group(group N,n=8).Group C was challenged with passive cigarette smokingand intratracheal instillation of lipopolysaccharide.Six weeks later pulmonary functions were tested,bronchoalveolar fluidand arterial blood gases were assayed,and histopathological evaluations were performed in turn.The expressions ofTACE,TNF-α and ErbB3 in lungs of all rats were determined histochemically.Results The expressions of TACE,TNF-α and ErbB3 were significantly higher in group C than in group N(P<0.01).The contents of TNF-α in serum(P<0.01)and bronchoalveolar lavage fluid(BALF)(P<0.01)were elevated moresignificantly in group C than in group N.A positive correlation existed between TACE and TNF-α(r=0.784,P<0.01)andbetween TACE and ErbB3(r=0.526,P<0.01)respectively.Conclusions TNF-α and ErbB3 are involved in the pathogenesis of COPD.TACE contributes to the progress of COPDindirectly through the function of TNF-α and ErbB3.Chin Med J 2007;120(17):1505-1510 Background Chronic obstructive pulmonary disease (COPD) is associated not only with airway inflammation characterized by mucin hypersecretion but also with systemic inflammation. Tumor necrosis factor alpha (TNF-a) is foundto take part in systemic inflammation, and ErbB3 plays an important role in mucin hypersecretion of COPD. Since TNF-αconverting enzyme (TACE) is involved in the activation of both TNF-a and ErbB3, we established rat models of COPD to investigate the expressions of TACE, TNF-α and ErbB3 and to explore the correlations among TACE, TNF -α and ErbB3 probarently. Methods Thirty Wistar male rats were randomly divided into COPD group (group C, n = 10), saline solution parallelgroup (group P, n = 8), and normal control group (group N, n = 8). Group C was challenged with passive cigarette smoking and intratracheal instillation of lipopolysaccharide. Six weeks later pulmonary functions were tested, bronchoalveolar fluid and arterial blood gases were assayed, and histopathological evaluations were performed in The expressions of TACE, TNF-α and ErbB3 in lungs of all rats were determined histochemically. Results of the expressions of TACE, TNF-α and ErbB3 were significantly higher in group C than in group N (P <0.01). contents of TNF-αin serum (P <0.01) and bronchoalveolar lavage fluid (BALF) (P <0.01) were elevated more significantly in group C than in group NA positive correlation existed between TACE and TNF-α andbetween TACE and ErbB3 (r = 0.526, P <0.01) respectively.Conclusions TNF-α and ErbB3 are involved in the pathogenesis of COPD.TACE contributes to the progress of COPDindirectly through the function of TNF-α and ErbB3.Chin Med J 2007 ; 120 (17): 1505-1510
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