We assume that IL-8 and TGF-beta may act as key mediators for airway inflammation and fibroproliferation in the pathogenesis of OB, with bronchial epithelial cells serving as a relevant source of IL-8.
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)-b 1 had been found. The goal of the study was to evaluate whether TGF-b 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-b 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-b 1 induced a marked decrease in SLPI protein levels (1 ng . mL and NE also caused a significant reduction in SLPI synthesis (10 ng . mL -1 TGF-b 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-b 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-b 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-b 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. Eur Respir J 2000; 15: 1052±1057.
Obliterative bronchiolitis is commonly interpreted as chronic rejection and involves the bronchial and bronchiolar epithelium. Upregulation of major histocompatibility complex (MHC) II on bronchial epithelial cells (BEC) had been hypothesised to be an important trigger of a bronchus directed rejection response. More recently, the additional expression of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on antigen presenting cells were found to play an important role in the activation of T-lymphocytes in transplant rejection. The role of the expression of these molecules by BEC is unclear.BEC obtained by bronchial brushing and bronchoalveolar lavage fluid (BALF) cells from lung transplant recipients were studied and evaluated for messenger ribonucleic acid (mRNA) expression of B7-1 and B7-2 by semi-quantitative reverse transcriptasepolymerase chain reaction. Significantly elevated B7-1/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ratios were found in BEC from patients examined during the first 3 months after lung transplantation. Interestingly, in a small group of patients with bronchiolitis obliterans syndrome the B7-1/GAPDH and B7-2/GAPDH ratios were significantly elevated for BEC, whereas no differences were found for the BALF cells.In summary, B7 messenger ribonucleic acid expression by bronchial epithelial cells may play a role in (chronic) lung allograft rejection.
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