Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of apoptosis and the expression of Fas antigen (Fas)/Fas ligand (FasL) mRNA in bleomycin-induced pulmonary fibrosis in mice were examined. Male ICR mice were intratracheally instilled with bleomycin (5 U/kg of body weight). The controls were injected with sterile saline. The animals were anesthetized and killed at 1, 6, and 12 h, and 1, 3, 5, 7, 9, and 14 days after bleomycin instillation. We assessed the incidence of apoptosis in lung tissues by DNA fragmentation on agarose gel electrophoresis, terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling, and electron microscopy. The expression of Fas and FasL mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). The localization of Fas mRNA was analyzed by in situ hybridization and that of FasL mRNA was analyzed by RT in situ PCR. The results showed that (1) a single instillation of bleomycin leads to the rapid appearance of apoptosis in bronchial and alveolar epithelial cells, which resolves within 1 day, and (2) apoptosis reappears on day 7 and continues for over 14 days after bleomycin instillation. This was accompanied with a progression of fibrosis. Corticosteroid administration completely blocked both apoptosis and fibrosis. The expression of Fas mRNA was upregulated in the alveolar epithelial cells by the bleomycin instillation. FasL mRNA was also upregulated in infiltrating lymphocytes after bleomycin treatment, but not in the control mice. The administration of corticosteroids suppressed the expression of Fas and FasL mRNA as well as apoptosis and fibrosis. Although these results do not show that apoptosis mediated by the Fas/FasL system is directly linked to bleomycin-induced fibrosis, we speculate that excessive apoptosis and the Fas/FasL system play a role in the pathogenesis of bleomycin-induced lung injury.
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PMID:Apoptosis and expression of Fas/Fas ligand mRNA in bleomycin-induced pulmonary fibrosis in mice. 899 84

Fas antigen is a cell surface protein that mediates apoptosis, and it is expressed in various cells and tissues. Fas ligand binds to its receptor Fas, thus inducing apoptosis of Fas-bearing cells. Malfunction of the Fas-Fas ligand system causes lymphoproliferative disorders and autoimmune diseases, whereas its exacerbation may cause tissue destruction. We hypothesize that excessive apoptosis mediated by Fas-Fas ligand interaction may damage alveolar epithelial cells and result in pulmonary fibrosis. Mice were allowed to inhale repeatedly an aerosolized anti-Fas antibody for 14 days. The nuclei of bronchial and alveolar epithelial cells were positively stained by in situ DNA nick end labeling. Electron microscopy demonstrated apoptotic changes in bronchial and alveolar epithelial cells. Histologic findings and hydroxyproline content showed the development of pulmonary fibrosis, which was dependent on the dose of anti-Fas antibody. The repeated inhalation of control antibody (isotype-matched control hamster IgG) did not induce apoptosis of epithelial cells or pulmonary fibrosis. The expression of TGF-beta mRNA was upregulated from day 7 to day 28 in lung tissues of anti-Fas antibody-treated mice but not in those of control mice. In this report, we present the evidence that repeated inhalation of anti-Fas antibody mimicking Fas-Fas ligand crosslinking induces excessive apoptosis and inflammation, which results in pulmonary fibrosis in mice.
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PMID:Induction of apoptosis and pulmonary fibrosis in mice in response to ligation of Fas antigen. 930 12

Pulmonary fibrosis begins with alveolitis, which progresses to destruction of lung tissue and excess collagen deposition. This process could be the result of DNA damage and a form of apoptosis. Therefore, we hypothesized that Fas ligand (FasL), which induces apoptosis in cells expressing Fas antigen (Fas), is associated with pulmonary fibrosis. We examined frozen lung tissues from seven patients with idiopathic pulmonary fibrosis (IPF), and bronchoalveolar lavage fluid (BALF) cells from 19 patients with IPF and from 17 patients with interstitial pneumonia associated with collagen vascular diseases (CVD-IP). We used five frozen lungs with normal lung parenchyma and BALF cells from 10 patients with solitary pulmonary nodule as controls. Reverse transcription-polymerase chain reaction (RT-PCR) showed that FasL messenger RNA (mRNA) was expressed in BALF cells from all patients with IPF and from 15 of 16 patients with CVD-IP. FasL mRNA was not detected in BALF cells except in one of 10 controls. RT in situ PCR detected FasL mRNA in inflammatory cells in BALF from patients with IPF. Immunohistochemistry detected FasL protein in infiltrating lymphocytes and granulocytes in all of seven frozen lung tissues of IPF, but in none of five control lung tissues. Additionally, the expression of Fas appeared to be upregulated in bronchiolar and alveolar epithelial cells in IPF compared with normal lung parenchyma by immunohistochemistry. We conclude that Fas and FasL were upregulated in fibrosing lung diseases and may associate with DNA damage or apoptosis of bronchiolar and alveolar epithelial cells in this disorder.
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PMID:The involvement of Fas-Fas ligand pathway in fibrosing lung diseases. 987 Sep 17

The Fas ligand is predominantly expressed in activated T lymphocytes and is one of the major effector molecules of cytotoxic T lymphocytes and natural killer cells. Previously, we found excessive apoptosis of epithelial cells and infiltrating lymphocytes expressing Fas ligand mRNA in the lung tissue of bleomycin-induced pulmonary fibrosis in mice. Here we demonstrated that the administration of a soluble form of Fas antigen or anti-Fas ligand antibody prevented the development of this model and that lpr and gld mice were resistant against the induction of pneumopathy. These results suggest that the Fas-Fas ligand pathway plays an essential role in the development of pulmonary fibrosis and that preventing this pathway could have therapeutic value in lung injury and fibrosis.
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PMID:Essential roles of the Fas-Fas ligand pathway in the development of pulmonary fibrosis. 1039 91

Different defects in Fas/APO-1 interaction with its ligand or in signaling of apoptosis may contribute to autoimmune disease. The aim of this study was to examine whether elevated serum-soluble Fas (sFas) levels are associated with rheumatoid arthritis (RA) or systemic sclerosis (SSc). sFas level was assayed using a sandwich ELISA in serum from 37 patients with RA, 30 patients with SSc and 20 healthy controls. The RA patients were classified according to disease activity, anatomical joint damage, and the presence of pulmonary involvement. Presence of pulmonary fibrosis, CO diffusion capacity (DLCO) and skin score were determined in patients with SSc. Serum sFas levels were not significantly different between study groups. Serum sFas level in the active RA patients was significantly higher than in the patients with inactive disease (p < 0.05). The untreated active RA patients had significantly higher sFas level than healthy controls (p < 0.05). In RA patients, sFas level was significantly correlated with rheumatoid factor titer (p = 0.01), C-reactive protein (p < 0.05), and erythrocyte sedimentation rate (p < 0.05). The RA patients with severe joint damage had significantly higher sFas level than those with mild joint damage (p < 0.05). The untreated SSc patients had significantly higher sFas levels than the treated SSc patients and healthy controls (p < 0.01). Serum sFas level was not correlated with presence of pulmonary fibrosis, DLCO or skin score. The soluble Fas molecule may provide a useful additional marker for assessment of disease activity and severity in patients with RA.
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PMID:The levels of serum-soluble Fas in patients with rheumatoid arthritis and systemic sclerosis. 1545 14