Open Respiratory Medicine Journal最新文献

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The Role of Sphingolipids and Ceramide in Pulmonary Inflammation in Cystic Fibrosis 鞘脂和神经酰胺在囊性纤维化肺部炎症中的作用

Open Respiratory Medicine Journal Pub Date : 2010-03-30 DOI: 10.2174/1874306401004010039

K. A. Becker, J. Riethmüller, Yang Zhang, E. Gulbins

{"title":"The Role of Sphingolipids and Ceramide in Pulmonary Inflammation in Cystic Fibrosis","authors":"K. A. Becker, J. Riethmüller, Yang Zhang, E. Gulbins","doi":"10.2174/1874306401004010039","DOIUrl":"https://doi.org/10.2174/1874306401004010039","url":null,"abstract":"Sphingolipids and in particular ceramide have been shown to be critically involved in the response to many receptor-mediated, but also receptor-independent, mainly stress stimuli. Recent studies demonstrate that ceramide plays an important role in the pathogenesis of cystic fibrosis, a hereditary metabolic disorder caused by mutations of the Cystic Fibrosis Transmembrane Conductance Regulator. Patients with cystic fibrosis suffer from chronic pulmonary inflammation and microbial lung infections, in particular with Pseudomonas aeruginosa. Chronic pulmonary inflammation in these patients seems to be the initial pathophysiological event. Inflammation may finally result in the high infection susceptibility of these patients, fibrosis and loss of lung function. Recent studies demonstrated that ceramide accumulates in lungs of cystic fibrosis mice and causes age-dependent pulmonary inflammation as indicated by accumulation of neutrophils and macrophages in the lung and increased pulmonary concentrations of Interleukins 1 and 8, death of bronchial epithelial cells, deposition of DNA in bronchi and high susceptibility to Pseudomonas aeruginosa infections. Genetic or pharmacological inhibition of the acid sphingomyelinase blocks excessive ceramide production in lungs of cystic fibrosis mice and corrects pathological lung findings. First clinical studies confirm that inhibition of the acid sphingomyelinase with small molecules might be a novel strategy to treat patients with cystic fibrosis.","PeriodicalId":39127,"journal":{"name":"Open Respiratory Medicine Journal","volume":"44 1","pages":"39 - 47"},"PeriodicalIF":0.0,"publicationDate":"2010-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68068057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 14

Antiproteases as Therapeutics to Target Inflammation in Cystic Fibrosis 抗蛋白酶作为治疗囊性纤维化靶炎症的药物

Open Respiratory Medicine Journal Pub Date : 2010-03-30 DOI: 10.2174/1874306401004010020

D. Quinn, S. Weldon, C. Taggart

{"title":"Antiproteases as Therapeutics to Target Inflammation in Cystic Fibrosis","authors":"D. Quinn, S. Weldon, C. Taggart","doi":"10.2174/1874306401004010020","DOIUrl":"https://doi.org/10.2174/1874306401004010020","url":null,"abstract":"Cystic Fibrosis (CF) is the most common fatal inherited disease of Caucasians, affecting about 1 in 3000 births. Patients with CF have a recessive mutation in the gene encoding the CF transmembrane conductance regulator (CFTR). CFTR is expressed in the epithelium of many organs throughout the exocrine system, however, inflammation and damage of the airways as a result of persistent progressive endobronchial infection is a central feature of CF. The inflammatory response to infection brings about a sustained recruitment of neutrophils to the site of infection. These neutrophils release various pro-inflammatory compounds including proteases, which when expressed at aberrant levels can overcome the endogenous antiprotease defence mechanisms of the lung. Unregulated, these proteases can exacerbate inflammation and result in the degradation of structural proteins and tissue damage leading to bronchiectasis and loss of respiratory function. Other host-derived and bacterial proteases may also contribute to the inflammation and lung destruction observed in the CF lung. Antiprotease strategies to dampen the excessive inflammatory response and concomitant damage to the airways remains an attractive therapeutic option for CF patients.","PeriodicalId":39127,"journal":{"name":"Open Respiratory Medicine Journal","volume":"4 1","pages":"20 - 31"},"PeriodicalIF":0.0,"publicationDate":"2010-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1874306401004010020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68068006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

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