Expression of transforming growth factor beta1 in bronchial biopsies in asthma and COPD.

Department of Pulmonary Medicine, Gazi University School of Medicine, Ankara, Turkey.
Journal of Asthma (Impact Factor: 1.8). 01/2004; 40(8):887-93.
Source: PubMed


The role of transforming growth factor beta1 (TGF beta1) in airway remodeling in asthma and chronic obstructive pulmonary disease (COPD) has not been fully described. To evaluate the possible pathogenetic role of TGF beta1 in asthma and COPD, immunohistochemical expression of TGF beta1 was described in bronchial biopsies from patients with asthma and COPD compared with healthy individuals. Twelve subjects with asthma, 13 subjects with COPD, and 10 healthy individuals enrolled in the study. Bronchial biopsies were stained with hematoxylin and eosin and anti-TGF beta1 antibody. As a result, immunoreactive TGF beta1 was mainly localized in association with connective tissue in all groups. The staining intensity was not statistically different among the groups in bronchial epithelium, whereas it was significantly higher in the group of asthma in the submucosa. Because there is evidence showing a significant increase of staining intensity in the submucosa from asthmatics but not from subjects with COPD, we may conclude that TGF beta1 may play a significant role in pathogenesis of asthma but not in COPD.

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    • "Notably, TGF-β1 is involved in remodeling processes in COPD through an activation of fibroblasts and induction of ECM production and may regulate proteoglycan synthesis [17,29]. TGF-β1 expression has previously been shown to be increased in central airways [30] and in peripheral blood [31] from COPD patients. Also, fibroblasts from peribronchiolar areas of lung tissue from patients with severe emphysema have increased production of TGF-β1[32]. "
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    ABSTRACT: Prostacyclin analogs are potent vasodilators and possess anti-inflammatory properties. However, the effect of prostacyclin on extracellular matrix (ECM) in COPD is not well known. Collagen fibrils and proteoglycans are essential ECM components in the lung and fibroblasts are key players in regulating the homeostasis of ECM proteins. The aim was to study the synthesis of prostacyclin and its effect on fibroblast activity and ECM production, and in particular collagen I and the collagen-associated proteoglycans biglycan and decorin. Parenchymal lung fibroblasts were isolated from lungs from COPD patients (GOLD stage IV) and from lungs and transbronchial biopsies from control subjects. The prostacyclin analog iloprost was used to study the effect of prostacyclin on ECM protein synthesis, migration, proliferation and contractile capacity of fibroblasts. TGF-β1 stimulation significantly increased prostacyclin synthesis in fibroblasts from COPD patients (p < 0.01), but showed no effect on fibroblasts from control subjects. Collagen I synthesis was decreased by iloprost in both control and COPD fibroblasts (p < 0.05). Conversely, iloprost significantly altered biglycan and decorin synthesis in control fibroblasts, but iloprost displayed no effect on these proteoglycans in COPD fibroblasts. Proliferation rate was reduced (p < 0.05) and contractile capacity was increased in COPD fibroblasts (p < 0.05) compared to control fibroblasts. Iloprost decreased proliferative rate in control fibroblasts (p < 0.05), whereas iloprost attenuated contraction capacity in both COPD (p < 0.01) and control fibroblasts (p < 0.05). Iloprost reduced collagen I synthesis and fibroblast contractility but did not affect the collagen-associated proteoglycans or proliferation rate in fibroblasts from COPD patients. Enhanced prostacyclin production could lead to improper collagen network fibrillogenesis and a more emphysematous lung structure in severe COPD patients.
    Respiratory research 02/2013; 14(1):21. DOI:10.1186/1465-9921-14-21 · 3.09 Impact Factor
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    • "non-utilised) inflammatory cell-derived TGFβ1 was stored in the ECM after secretion and, as a result, would be responsible for the increased TGFβ1 expression observed at a time when cellular inflammation was resolved. Otherwise, increased TGFβ1 expression may be produced by airway structural cells present in the submucosa such as (myo)fibroblasts or ASM cells [62,69]. "
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    ABSTRACT: Asthma is a waxing and waning disease that leads to structural changes in the airways, such as subepithelial fibrosis, increased mass of airway smooth muscle and epithelial metaplasia. Such a remodeling of the airways further amplifies asthma symptoms, but its etiology is unknown. Transforming growth factor beta1 is a pleiotropic cytokine involved in many fibrotic, oncologic and immunologic diseases and is believed to play an essential role in airway remodeling that occurs in asthmatic patients. Since it is secreted in an inactive form, the overall activity of this cytokine is not exclusively determined by its level of expression, but also by extensive and complex post-translational mechanisms, which are all important in modulating the magnitude of the TGFbeta1 response. Even if TGFbeta1 upregulation in asthma is considered as a dogma by certain investigators in the field, the overall picture of the published literature is not that clear and the cellular origin of this cytokine in the airways of asthmatics is still a contemporaneous debate. On the other hand, it is becoming clear that TGFbeta1 signaling is increased in the lungs of asthmatics, which testifies the increased activity of this cytokine in asthma pathogenesis. The current work is an impartial and exhaustive compilation of the reported papers regarding the expression of TGFbeta1 in human asthmatics. For the sake of comparison, several studies performed in animal models of the disease are also included. Inconsistencies observed in human studies are discussed and conclusions as well as trends from the current state of the litterature on the matter are proposed. Finally, the different points of regulation that can affect the amplitude of the TGFbeta1 response are briefly revised and the possibility that TGFbeta1 is dysregulated at another level in asthma, rather than simply in its expression, is highlighted.
    Respiratory research 02/2007; 8(1):66. DOI:10.1186/1465-9921-8-66 · 3.09 Impact Factor
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    • "Immunohistochemical analysis was performed using an avidin—biotin—peroxidase technique (ABC method) as previously described [15]. Briefly, after deparaffinization and following rehydration , antigen retrieval with citrate buffer (pH 6) was performed according to the manufacturer's recommendation. "
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    ABSTRACT: Environmentally exposed erionite is a potent and unique inducer of malignant pleural mesothelioma (MPM) in Central Anatolia in Turkey. Previous studies have shown that erionite induced MPM has different biological behavior than asbestos induced MPM. Although impaired apoptosis has been implicated in tumor biology, the relationship between the type of environmental exposure and apoptosis has not yet been evaluated in MPM. The purpose of this study was to determine the expression of apoptosis regulating proteins and their prognostic significance in erionite and asbestos induced MPM. Thirty-five patients with MPM (16 erionite and 19 asbestos induced), and 17 patients with adenocarcinoma were comparatively evaluated. Expression of Bcl-2, Bax, Fas and Fas Ligand, were assessed by immunohistochemistry. Bcl-2 and Fas did not stain in almost all specimens. The staining extension of Bax was 13.75 +/- 19.27%, 5.89 +/- 14.51% and 7.38 +/- 14.53% for erionite and asbestos induced MPM and adenocarcinoma, respectively (p = 0.566). The staining extension of Fas Ligand was 26.87 +/- 31.87%, 46.10 +/- 37.30% and 26.47 +/- 23.23% for erionite and asbestos induced MPM, and adenocarcinoma, respectively (p = 0.123). Bax negative patients in erionite group had longer survival than Bax positive patients (18 months versus 14 months) (p = 0.06). Fas Ligand positive patients showed statistically better survival than Fas Ligand negative patients in all MPM group (15 months versus 12 months) (p = 0.05). Although all proteins expressed in similar extension in all samples, Bax staining displayed an inverse relation with survival in erionite group. This may implicate a difference in Bax functioning in erionite induced MPM. However, Fas Ligand may be functionally intact to reduce tumor survival.
    Lung Cancer 12/2005; 50(2):189-98. DOI:10.1016/j.lungcan.2005.05.025 · 3.96 Impact Factor
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