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Effects of hypoxia on dendritic cell biology : dottorato di ricerca in patologia e neuropatologia sperimentali : tesi di dottorato

Mancino, Alessandra <1979- >

Tesi o dissertazioni - 2009

Summary Low oxygen tension (hypoxia) is a common feature of several inflammatory conditions, such as infected tissues, wounds, rheumatic joints, and tumors, [1] and strongly affects the expression of specific genes involved in leukocyte activation and recruitment [2]. Due to energetic requirements cells localizing in hypoxic sites undergo to a metabolic adaptation program, whose major regulator is the Hypoxia-Inducible Factor-1alpha (HIF-1a) [3]. HIF-1a is constitutively expressed, but in normoxic conditions became hydroxylated by an oxygen-dependent prolyl-4-hydroxylases, that induces its degradation via proteasome. In contrast, in hypoxia this enzymatic reaction can’t occur and HIF-1a translocates to the nucleus, dimerizes with HIF-1beta (HIF-1b) and binds Hypoxic Responsible Elements (HRE) in the promoter of specific HIF-1 inducible genes [4, 5]. In sites of inflammation characterized by low oxygen tension, infiltrating leucocytes, including dendritic cells (DCs), have to move against [...]
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