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)

A major contributory factor to the development of chronic obstructive pulmonary disease (COPD) is the inflammatory response to cigarette smoke. However, when those with COPD stop smoking, a continuous cycle of inflammation can lead to continued decline in lung function. Understanding the role of inflammatory cells in COPD is difficult because it is a mixture of diseases--bronchitis, small airways disease and emphysema--that exhibit different patterns of inflammation and different pathology. Neutrophils and macrophages have been implicated in this process; they release proteolytic enzymes and generate oxidants, which cause tissue damage, as well as cytokines and chemokines, which can potentiate inflammation and trigger an immune response. Analysis of sputum and bronchoalveolar lavage fluid shows increases in both neutrophils and macrophages in respiratory secretions in COPD subjects; neutrophils are the predominant cell in the conducting airways, whereas macrophages are the major cell in secretions from the small airways and parenchyma. Airway tissue neutrophils are increased in the large and small airways during infection and exacerbations, whilst parenchymal neutrophil numbers are inversely related to alveolar wall destruction, suggesting that they are not involved in the progression of emphysema. Macrophages are increased throughout the respiratory tract airway lumen and epithelium in COPD and are positively related to severity of disease, airway obstruction and degree of alveolar wall damage in emphysema. Unactivated T-lymphocytes do not linger in lung tissue. Activated (eg due to antigenic stimulus) memory T cells home in to the lung and act as effector cells. CD-8+ T cell differentiation into memory cells is facilitated by CD4+ T cells. Binding of CD-8+ T cells to collagen stimulates proliferation and mediator production which may contribute to the inflammatory response. CD8+ cytotoxic/suppressor T cells release cytotoxic perforins and granzyme B which cause cell death and apoptosis, a feature of emphysema. Lung secretions contain only a small percentage of T cells; most T-lymphocytes reside in the subepithelial and smooth muscle region of the tissue. During COPD, there is either an increase in the CD8+/CD4+ ratio of T cells, or an increase in the in total numbers of both CD8+ and CD4+ T cells, in the tissue. Smoking status, smoking history, degree of airway obstruction and emphysema are all related to increased CD8+ cells and/or CD8+/CD4+ ratio. During severe emphysema requiring lung volume reduction surgery, there is a considerable increase in macrophages, neutrophils, eosinophils, CD4+ and CD8+ T cells which relates to the severity of the disease. Interestingly, the marked increase in luminal CD8+ cells results in an increased ratio of CD8+/CD4+ T cells that is not seen in the parenchymal tissue. The florid inflammation observed in severe emphysema is suggested to be related to latent viral infection.
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PMID:Inflammatory cells and chronic obstructive pulmonary disease. 1730 17

Chronic obstructive pulmonary disease (COPD) is a highly prevalent inflammatory lung condition characterized by airways disease and emphysema, and the precise mechanism of pathogenesis is poorly understood. The consistent features of COPD include protease-antiprotease imbalance, inflammation and accelerated aging caused by apoptosis or senescence. One family of molecules involved in all of these processes is the granzymes, serine proteases with the best-known member being granzyme B (GzmB). The majority of GzmB is released unidirectionally towards target cells, but GzmB can also be released nonspecifically and escape into the extracellular environment. GzmB is capable of cleaving extracellular matrix (ECM) proteins in vitro, and the accumulation of GzmB in the extracellular milieu during chronic inflammation in COPD could contribute to ECM degradation and remodelling and, consequently, the emphysematous phenotype in the lung. Preliminary studies suggest that increased GzmB expression is associated with increased COPD severity, and this may represent a promising new target for drug and biomarker discovery in COPD. In this paper, we review the potential pathogenic contributions of GzmB to the pathogenesis of COPD.
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PMID:The possible role of granzyme B in the pathogenesis of chronic obstructive pulmonary disease. 1963 69

Emphysema is a T-cell mediated autoimmune disease caused predominantly by cigarette smoking. Th17 cells and related cytokines may contribute to this disorder. However, the possible implication of Th17 cells in regulating inflammatory response in emphysema remains to be elucidated. In the current study, we tested the protein levels of IL-17 and IL-21 in peripheral blood and lung tissues from cigarette-smoke- (CS-) exposed mice and air-exposed mice, analyzed the frequencies of CD4(+)IL-17(+)(Th17) cells, IL-21(+)Th17 cells, and CD8(+)IL-21R(+) T cells in peripheral blood and lung tissues of mice, and their relationship with emphysematous lesions, and explored the impact of IL-21 on cytotoxic CD8(+) T cells function in vitro. It was found that the frequencies of Th17, IL-21(+)Th17, and CD8(+)IL-21R(+) T cells and the levels of IL-17 and IL-21 of CS-exposed mice were much higher than those of the air-exposed mice and correlated with emphysematous lesions. Additionally, the number of IL-21(+)Th17 cells positively correlated with the number of CD8(+)IL-21R(+) T cells. The in vitro experiments showed that IL-21 significantly augmented the secretion of perforin and granzyme B in CD8(+) T cells from CS-exposed mice. These data indirectly provide evidence that Th17 cells could be involved in the control of the local and system inflammatory response in emphysema by regulating CD8(+) cytotoxic T-cell function.
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PMID:Th17 cell enhances CD8 T-cell cytotoxicity via IL-21 production in emphysema mice. 2331 33