Expression of transforming growth factor beta1 in bronchial biopsies in asthma and COPD.
ABSTRACT 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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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 · 3.74 Impact Factor
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ABSTRACT: The transforming growth factor (TGF) superfamily encompasses about 30 members in mammals. The effect of TGF-beta subfamily members is exerted and regulated via selective pathways of synthesis and signaling that involve activation of latent TGF-beta, specific and high-affinity binding to cell membrane serine/threonine kinase receptors, activation of intracellular cascades that include Smad molecules and mitogen-activated protein kinases, and regulated termination of the effect by diverse mechanisms including protein degradation and transcriptional activation. Several comprehensive reviews on TGF-beta biology in general and on the role of this cytokine in other diseases have been published recently. In recent years an unexpected role of TGF-beta on lung homeostasis has been revealed. Here, we discuss the contribution of TGF-beta to the pathogenesis of asthma and chronic obstructive pulmonary disease, two common illnesses of the lung, as well as of lymphangioleiomyomatosis, a rare disease in women. The information we collate and integrate places TGF-beta at a pivotal point within complex networks that control lung physiology as well as the physiopathology of these lung diseases.Cell Biochemistry and Biophysics 02/2005; 43(1):131-48. DOI:10.1385/CBB:43:1:131 · 2.38 Impact Factor
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ABSTRACT: The molecular mechanisms by which bradykinin induces excessive airway obstruction in asthmatics remain unknown. Transforming growth factor (TGF)-beta has been involved in regulating airway inflammation and remodeling in asthma, although it is unknown whether TGF-beta can modulate bradykinin-associated bronchial hyperresponsiveness. To test whether TGF-beta directly modulates airway smooth muscle (ASM) responsiveness to bradykinin, isolated murine tracheal rings were used to assess whether TGF-beta alters ASM contractile responsiveness to bradykinin. Interestingly, we found TGF-beta-treated murine rings (12.5 ng/ml, 18 h) exhibited increased expression of bradykinin 2 (B(2)) receptors and became hyperreactive to bradykinin, as shown by increases in maximal contractile responses and receptor distribution. We investigated the effect of TGF-beta on bradykinin-evoked calcium signals since calcium is a key molecule regulating ASM excitation-contraction coupling. We reported that TGF-beta, in a dose- (0.5-10 ng/ml) and time- (2-24 h) dependent manner, increased mRNA and protein expression of the B(2) receptor in cultured human ASM cells. Maximal B(2) receptor protein expression that colocalized with CD44, a marker of membrane cell surface, occurred after 18 h of TGF-beta treatment and was further confirmed using fluorescence microscopy. TGF-beta (2.5 ng/ml, 18 h) also increased bradykinin-induced intracellular calcium mobilization in fura-2-loaded ASM cells. TGF-beta-mediated enhancement of calcium mobilization was not attenuated with indomethacin, a cyclooxygenase inhibitor. These data demonstrate for the first time that TGF-beta may play a role in mediating airway hyperresponsiveness to bradykinin seen in asthmatics by enhancing ASM contractile responsiveness to bradykinin, possibly as a result of increased B(2) receptor expression and signaling.AJP Lung Cellular and Molecular Physiology 11/2005; 289(4):L511-20. DOI:10.1152/ajplung.00027.2005 · 4.04 Impact Factor