HIF-1alpha and infectious diseases: a new frontier for the development of new therapies

• Published in: Revista do Instituto de Medicina Tropical de São Paulo
• Main Authors: Sânia Alves dos Santos, Dahir Ramos de Andrade Júnior
• Format: Article in Journal/Newspaper
• Language: English
• Published: Universidade de São Paulo (USP) 2017
• Subjects: HIF-1alpha; Hypoxia; Bacteria; Sepsis; Virus; Parasites; Fungi; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1590/s1678-9946201759092; https://doaj.org/article/4979be7c184949ffa3b731b2978e1828

ABSTRACT The aim of this review is to show the significant role of HIF-1alpha in inflammatory and infectious diseases. Hypoxia is a physiological characteristic of a wide range of diseases from cancer to infection. Cellular hypoxia is sensed by oxygen-sensitive hydrolase enzymes, which control the protein stability of hypoxia-inducible factor alpha 1 (HIF-1alpha) transcription factors. When stabilized, HIF-1alpha binds with its cofactors to HIF-responsive elements (HREs) in the promoters of target genes to organize a broad ranging transcriptional program in response to the hypoxic environment. HIF-1alpha also plays a regulatory function in response to a diversity of molecular signals of infection and inflammation even under normoxic conditions. HIF-1alpha is stimulated by pro-inflammatory cytokines, growth factors and a wide range of infections. Its induction is a general element of the host response to infection. In this review, we also discuss recent advances in knowledge on HIF-1alpha and inflammatory responses, as well as its direct influence in infectious diseases caused by bacteria, virus, protozoan parasites and fungi.