Asthma Ipf gene

Genetic background is a known predisposing risk factor for many acute and chronic pulmonary disorders and responses to environmental oxidants. Variation in lung injury responses to oxidative stimuli such as ozone, particles, hyperoxia, and chemotherapeutic agents between genetically standardized inbred mouse strains has been demonstrated. In this review, we discuss quantitative trait loci (QTLs) which contain candidate genes that confer differential susceptibility to oxidative stimuli between strains in mouse models of airway toxicity and disease...

Recently DNA mismatch repair system (MMR) has been extensively investigated in molecular medicine. Microsatellite (MS) DNA alterations are considered as indicating an ineffective MMR system. MS loss of heterozygosity (LOH) and microsatellite instability (MSI) have been reported in a number of human malignancies. LOH and MSI have recently been detected in benign diseases, such as actinic keratosis, pterygium and atherosclerosis. In addition, MSI and LOH have been detected in asthma, chronic obstructive pulmonary disease, sarcoidosis and idiopathic pulmonary fibrosis...

TARC (CCL17) and MDC (CCL22) are well-known chemoattractants for Th2 cells. Here, we evaluated the role of both chemokines for cigarette smoke-induced airway inflammation. The expression profiles of MDC, TARC, and their receptor CCR4 were analyzed in models of acute and chronic cigarette smoke-induced airway inflammation that is characterized by a Th1 immune response. The results were compared to the expression of both chemokines in models of idiopathic pulmonary fibrosis and acute asthma, which are associated with a Th2 immune response...

The lungs are directly exposed to higher oxygen concentrations than most other tissues. Increased oxidative stress is a significant part of the pathogenesis of obstructive lung diseases such as asthma and chronic obstructive pulmonary disease, parenchymal lung diseases (e.g., idiopathic pulmonary fibrosis and lung granulomatous diseases), and lung malignancies. Lung tissue is protected against these oxidants by a variety of antioxidant mechanisms among which the superoxide dismutases (SODs) are the only ones converting superoxide radicals to hydrogen peroxide...

Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance, a major cause of cell damage. The development of an oxidant/antioxidant imbalance in lung inflammation may activate redox-sensitive transcription factors such as nuclear factor-KB, and activator protein-1 (AP-1), which regulate the genes for pro-inflammatory mediators and protective antioxidant genes. Glutathione (GSH), a ubiquitous tripeptide thiol, is a vital intra- and extracellular protective antioxidant against oxidative/nitrosative stresses, which plays a key role in the control of pro-inflammatory processes in the lungs...

Recently acquired insights into the complex functions of the immune system in the airways and lungs shed new light on the importance of local immunologic defence mechanisms in the maintenance of a normal lung function. Prolonged exposure to inhaled allergens or to aspecific injurious substances in the environment, in particular, may give rise to the onset of immunopathology that may manifest itself only years later. Clinically, the most common of such diseases is allergic asthma. This results from the interaction of an unknown number of genes with specific and aspecific environmental factors...

There is increasing evidence implicating activated macrophages in the pathogenesis of interstitial and other lung diseases. We investigated whether there was a unique pattern of cell surface expression that constituted a disease-specific phenotype on alveolar macrophages from patients with interstitial lung disease (ILD). Macrophage cell surface receptor expression of 19 selected markers was assessed by indirect immunofluorescence and flow cytometry in bronchoalveolar lavage (BAL) fluids from patients with idiopathic pulmonary fibrosis (IPF, n = 4), scleroderma (SCL-ILD, n = 14), mild asthma (n = 7), allergy without asthma (n = 2), and normal subjects (n = 9)...

An influx of eosinophils into the lungs occurs in several pulmonary disorders. However, the mechanisms involved remain unknown. Lung epithelial cell release of eosinophil chemotactic factors such as RANTES or macrophage inflammatory protein-1 alpha (MIP-1 alpha) could account for the influx of eosinophils into the lungs. In order to demonstrate the potential role for lung epithelial cells to release RANTES and/or MIP-1 alpha, we investigated the mRNA expression and protein release in cultured A549 cells. Tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) induced a time- and dose-dependent increase in RANTES mRNA expression and protein release...