Expressions of tumor necrosis factor-converting enzyme and ErbB3 in rats with chronic obstructive pulmonary disease.
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-alpha) is found to take part in systemic inflammation, and ErbB3 plays an important role in mucin hypersecretion of COPD. Since TNF-alpha converting enzyme (TACE) is involved in the activation of both TNF-alpha and ErbB3, we established rat models of COPD to investigate the expressions of TACE, TNF-alpha and ErbB3 and to explore the correlations among TACE, TNF-alpha and ErbB3 respectively.


METHODS
Thirty Wistar male rats were randomly divided into COPD group (group C, n = 10), saline solution parallel group (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 turn. The expressions of TACE, TNF-alpha and ErbB3 in lungs of all rats were determined histochemically.


RESULTS
The expressions of TACE, TNF-alpha and ErbB3 were significantly higher in group C than in group N (P < 0.01). The contents of TNF-alpha in serum (P < 0.01) and bronchoalveolar lavage fluid (BALF) (P < 0.01) were elevated more significantly in group C than in group N. A positive correlation existed between TACE and TNF-alpha (r = 0.784, P < 0.01) and between TACE and ErbB3 (r = 0.526, P < 0.01) respectively.


CONCLUSIONS
TNF-alpha and ErbB3 are involved in the pathogenesis of COPD. TACE contributes to the progress of COPD indirectly through the function of TNF-alpha and ErbB3.
Ju
Chun-rong
CR
Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510120, China. juchunrongju@163.com
Xia
Xi-zheng
XZ
Chen
Rong-chang
RC
D051722:ADAM Proteins / Q000032:analysis* / Q000502:physiology; D000072198:ADAM17 Protein; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D007150:Immunohistochemistry; D008168:Lung / Q000503:physiopathology; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020893:Receptor, ErbB-3 / Q000032:analysis* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D014409:Tumor Necrosis Factor-alpha; D020893:Receptor, ErbB-3; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606464:Adam17 protein, rat