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)

Bleomycin-induced cytotoxicity is believed to be caused by single- and double-strand DNA breaks. To examine the effect of bleomycin on DNA strand breaks and the role of these breaks in bleomycin induced pulmonary fibrosis in mice, we analyzed DNA strand breaks in situ by TdT-mediated dUTP-biotin nick end labeling (TUNEL), previously described by Gavrieli et al. The nuclei of bronchiolar epithelial cells were strongly stained 1 hr to 12 hr after bleomycin administration, and after that period DNA damage was repaired. Nuclei of alveolar epithelial cells showed positive signals correlated with progression of fibrosis. Although corticosteroids did not block the early DNA damage in bronchiolar epithelial cells, they did inhibit later damage to alveolar epithelial cells and fibrosis. We speculate that the DNA damage in alveolar epithelial cells and the progression of fibrosis in later stages are associated with inflammatory cytokines. These findings show the location and the time course of the DNA damage in bleomycin-induced pneumonitis in mice, and they indicate that the prolongation of DNA damage in alveolar epithelial cells is closely related to fibrinogenesis.
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PMID:[DNA strand breaks in epithelial cells from mice with bleomycin induced pulmonary fibrosis]. 871 84

Apoptosis was measured in rat alveolar macrophage NR8383 cells challenged in vitro with respirable quartz or kaolin dust and with the dusts pretreated with dipalmitoyl phosphatidylcholine (DPPC) to model conditioning of respired dusts by interaction with a primary phospholipid component of pulmonary surfactant. Quartz dust is known to induce apoptosis in vitro and in vivo. For this study, quartz and kaolin were compared as dusts of similar cytotoxicity in some in vitro assays but of differing pathogenic potential: quartz can cause significant pulmonary fibrosis while kaolin generally does not. NR8383 cells exposed to native quartz at concentrations from 50 to 400 microg/ml for 6 h showed a dose-dependent increase in apoptosis measured by the TdT-mediated dUTP-fluorescein nick end labeling (TUNEL), cell death ELISA, and DNA ladder formation assays, while native kaolin induced significant response only at the higher concentrations and only in the TUNEL and ELISA assays. For cell challenge from 6 h to 5 days at 100 microg/ml of dust, quartz was active at all times while kaolin was active only at 5 days. DPPC pre-treatment suppressed quartz activity until 3 days and kaolin activity through 5 days. Cellular release of lactate dehydrogenase, measured in parallel experiments to compare dust apoptotic and necrotic activities, indicated that components of serum as well as surfactant may affect kaolin in vitro expression of those activities.
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PMID:Effects of phospholipid surfactant on apoptosis induction by respirable quartz and kaolin in NR8383 rat pulmonary macrophages. 1155 20

Amphiregulin, an EGF receptor (EGFR) ligand, is essential for epithelial development in various organs. A recent report suggested that amphiregulin acts as a protective factor in a liver injury model. Little is known about the roles of amphiregulin in lung injury and pulmonary fibrosis. The purpose of the present study was to investigate the role of amphiregulin in an experimental model of bleomycin-induced pneumopathy in mice. C57BL/6 mice were administered a bleomycin hydrochloride solution intratracheally. Recombinant human amphiregulin was injected intraperitoneally at 6, 8, 10, and 12 days after the bleomycin instillation. The grades of inflammation and fibrosis were assessed histologically and biochemically, and the numbers of apoptotic cells were counted after TdT-mediated dUTP nick end labeling (TUNEL) staining in the lung tissues. We also examined downstream survival signals of EGFR, namely phosphorylated Akt and phosphorylated Erk, in lung tissues by Western blotting analysis and immunohistochemistry. Expression of intrinsic amphiregulin was increased in murine lung tissues after bleomycin instillation. Administration of recombinant amphiregulin improved the survival rate and suppressed the degrees of inflammation and fibrosis and the number of TUNEL-positive cells in lung tissues. Amphiregulin treatment enhanced the activation of Akt and Erk in lung epithelial cells. Amphiregulin may play a protective role in bleomycin-induced pneumopathy in mice, probably through the activation of survival signals. Administration of amphiregulin may be a novel therapeutic strategy against lung injury and fibrosis.
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PMID:Amphiregulin attenuates bleomycin-induced pneumopathy in mice. 1991 56