Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lung disease is the leading and second-leading cause of death in women and men in Taiwan, respectively. Epidemiological studies conducted in Taiwan have shown that cigarette smoking is the principal risk factor of lung disease, but little is known about the association between apoptosis and cigarette smoke (CS)-induced lung pathogenesis. We designed an animal exposure system to study signal proteins involved in the process of apoptosis induced by smoking in rat terminal bronchiole. Rats were exposed to CS in doses of 5, 10, and 15 cigarettes, respectively, and the exposure lasted for 30 min, twice a day, 6 days a week for 1 month. Following which the rats were sacrificed and the lung tissues were analyzed by histopathological methods. The terminal bronchioles revealed mild to severe inflammation according to the doses of CS and marked lipid peroxidation, lymphocyte infiltration, congestion, and epithelial emphysema of alveolar spaces were also noted. Using an in situ cell death detection kit (TA300), the association of CS with apoptosis was determined in a concentration-dependent manner. Immunohistochemical evaluation showed that CS treatment produced an increase in the cellular levels of Bax, t-Bid, cleaved caspase-3, phospho-p53, phospho-JNK, and FasL but a decline in Bcl-2 and Mcl-1 (p<0.001 for all) in rat terminal bronchioles. The results provided evidences suggesting that exposure to CS not only induced apoptosis, but also involved p53/Bax and JNK/FasL cascade pathway.
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PMID:Immunohistochemical detection of apoptotic proteins, p53/Bax and JNK/FasL cascade, in the lung of rats exposed to cigarette smoke. 1634 95

A disintegrin and metalloproteinase domain-15 (ADAM15) is expressed by cells implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD), but its contributions to COPD are unknown. To address this gap, ADAM15 levels were measured in samples from cigarette smoke (CS)-versus air-exposed wild-type (WT) mice. CS-induced COPD-like disease was compared in CS-exposed WT, Adam15-/-, and Adam15 bone marrow chimeric mice. CS exposure increased Adam15 expression in lung macrophages and CD8+ T cells and to a lesser extent in airway epithelial cells in WT mice. CS-exposed Adam15-/- mice had greater emphysema, small airway fibrosis, and lung inflammation (macrophages and CD8+ T cells) than WT mice. Adam15 bone marrow chimera studies revealed that Adam15 deficiency in leukocytes led to exaggerated pulmonary inflammation and COPD-like disease in mice. Adam15 deficiency in CD8+ T cells was required for the exaggerated pulmonary inflammation and COPD-like disease in CS-exposed Adam15-/- mice (as assessed by genetically deleting CD8+ T cells in Adam15-/- mice). Adam15 deficiency increased pulmonary inflammation by rendering CD8+ T cells and macrophages resistant to CS-induced activation of the mitochondrial apoptosis pathway by preserving mTOR signaling and intracellular Mcl-1 levels in these cells. These results strongly link ADAM15 deficiency to the pathogenesis of COPD.
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PMID:A disintegrin and metalloproteinase domain-15 deficiency leads to exaggerated cigarette smoke-induced chronic obstructive pulmonary disease (COPD)-like disease in mice. 3269 Aug 71