Open AccessTransforming growth factor‐β 1 is a potent inhibitor of secretory leukoprotease inhibitor expression in a bronchial epithelial cell line
Author(s) -
Jaumann F.,
Elssner A.,
Mazur G,
Dobmann S,
Vogelmeier C
Publication year - 2000
Publication title -
european respiratory journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.021
H-Index - 241
eISSN - 1399-3003
pISSN - 0903-1936
DOI - 10.1034/j.1399-3003.2000.01513.x
Subject(s) - slpi , neutrophil elastase , messenger rna , bronchoalveolar lavage , microbiology and biotechnology , elastase , transforming growth factor , gene expression , biology , incubation , cell culture , andrology , endocrinology , medicine , chemistry , lung , enzyme , immunology , gene , inflammation , biochemistry , genetics
Obliterative bronchiolitis (OB) is the major long‐term complication following lung and heart‐lung transplantation. In bronchoalveolar lavage fluid samples obtained from patients suffering from OB, a marked increase in the number of neutrophils and elevated expression of transforming growth factor (TGF)‐β 1 had been found. The goal of the study was to evaluate whether TGF‐β 1 is capable of interfering with the expression of the secretory leukoprotease inhibitor (SLPI), the dominating defence of the conducting airways against neutrophil elastase (NE). The authors analysed the effects of TGF‐β 1 on gene expression and protein release of SLPI by cultured human bronchial epithelial (BEAS‐2B) cells. SLPI protein levels in the supernatants were quantified with a specific enzyme‐linked immunosorbent assay; SLPI messenger ribonucleic acid (mRNA) levels were measured by reverse transcriptase polymerase chain reaction. Incubation with TGF‐β 1 induced a marked decrease in SLPI protein levels (1 ng·mL ‐1 TGF‐β 1 : stimulation index (SI; protein: relation to SLPI protein release of resting cells) = 0.56; 10 ng·mL ‐1 TGF‐β 1 : SI = 0.48; 50 ng·mL ‐1 TGF‐β 1 : SI = 0.37, p<0.01 each) and mRNA expression (1 ng·mL ‐1 TGF‐β 1 : SI (SI mRNA: relation to SLPI mRNA expression of resting cells) = 0.46; 10 ng·mL ‐1 TGF‐β 1 : SI=0.31; 50 ng·mL ‐1 TGF‐β 1 : SI=0.18, p<0.01 each) in a dose dependent fashion. Simultaneous incubation of BEAS‐2B cells with TGF‐β 1 and NE also caused a significant reduction in SLPI synthesis (10 ng·mL ‐1 TGF‐β 1 + 7.5 U·mL ‐1 NE: mRNA SI = 0.61, p<0.05; protein SI = 0.65, p<0.05; 50 ng·mL ‐1 TGF‐β 1 + 7.5 U·mL ‐1 NE: mRNA SI = 0.52, p<0.05; protein SI = 0.58, p<0.05; 10 ng·mL ‐1 TGF‐β 1 : mRNA SI = 0.33, p<0.01; protein SI = 0.38, p<0.01). In conclusion, the data suggest that the coincidence of neutrophilia and upregulation of transforming growth factor‐β 1 in obliterative bronchiolitis may lead to uninhibited neutrophil elastase activity by downregulation of secretory leukoprotease inhibitor, with the consequence of ongoing injury to the epithelium.