Y box-binding factor promotes eosinophil survival by stabilizing granulocyte-macrophage colony-stimulating factor mRNA.
نویسندگان
چکیده
Short-lived peripheral blood eosinophils are recruited to the lungs of asthmatics after allergen challenge, where they become long-lived effector cells central to disease pathophysiology. GM-CSF is an important cytokine which promotes eosinophil differentiation, function, and survival after transit into the lung. In human eosinophils, GM-CSF production is controlled by regulated mRNA stability mediated by the 3' untranslated region, AU-rich elements (ARE). We identified human Y box-binding factor 1 (YB-1) as a GM-CSF mRNA ARE-specific binding protein that is capable of enhancing GM-CSF-dependent survival of eosinophils. Using a transfection system that mimics GM-CSF metabolism in eosinophils, we have shown that transduced YB-1 stabilized GM-CSF mRNA in an ARE-dependent mechanism, causing increased GM-CSF production and enhanced in vitro survival. RNA EMSAs indicate that YB-1 interacts with the GM-CSF mRNA through its 3' untranslated region ARE. In addition, endogenous GM-CSF mRNA coimmunoprecipitates with endogenous YB-1 protein in activated eosinophils but not resting cells. Thus, we propose a model whereby activation of eosinophils leads to YB-1 binding to and stabilization of GM-CSF mRNA, ultimately resulting in GM-CSF release and prolonged eosinophil survival.
منابع مشابه
GM-CSF regulation in eosinophils.
Allergic asthma is characterized by a temporally and quantitatively inappropriate immunologic response. One of the hallmarks of this response is the accumulation of eosinophils in the airway and lung parenchyma, which results in broncho-constriction, lung damage and, ultimately, fibrosis. Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a pivotal role in this process by modulatin...
متن کاملMast cells enhance eosinophil survival in vitro: role of TNF-alpha and granulocyte-macrophage colony-stimulating factor.
Mast cell-eosinophil interactions in allergy have not yet been completely defined. To determine whether mast cells influence eosinophil survival, human peripheral blood eosinophils were incubated with rat peritoneal mast cell sonicate. After 3 days, viable eosinophils in medium were 21.3% compared with 44% with mast cell sonicate. Like sonicate, supernatants of compound 48/80-activated mast cel...
متن کاملCell cultures from bronchial subepithelial myofibroblasts enhance eosinophil survival in vitro.
Mechanisms of eosinophil accumulation and activation in the bronchial mucosa are crucial for the pathogenesis of asthma. The location of specialized fibroblasts, myofibroblasts, beneath the bronchial basement membrane and their proximity to infiltrating eosinophils potentially enable the myofibroblasts to modulate eosinophil survival and function in asthma. The aim of this study was to investig...
متن کاملFK506 and cyclosporin A inhibit granulocyte/macrophage colony-stimulating factor production by mononuclear cells in asthma.
Bronchial asthma is associated with eosinophilic inflammation and expression of T-cell-derived cytokines, which influence eosinophilic function. FK506, a newly established immunosuppressive agent, may have potential as a therapeutic instrument for asthma because of its suppressive effect on T-cell activation. To assess this, we compared the inhibitory effects of FK506 and cyclosporin A on produ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of immunology
دوره 167 10 شماره
صفحات -
تاریخ انتشار 2001