Hypoxia-inducible factor 1 alpha (HIF-1¿) and metabolic and inflammatory changes in macrophages cultured in a hypoxic environment

• Grant number: 24/17571-5
• Support Opportunities: Scholarships in Brazil - Program to Stimulate Scientific Vocations
• Start date: January 06, 2025
• End date: February 20, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Letícia da Rocha Pereira Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The hypoxic response in cells and tissues is mediated by hypoxia-inducible transcription factors (HIF), among which HIF-1¿ plays a key role in metabolic changes in response to oxygen availability. Macrophages, cells of the immune system, are present in all tissues of the body and accumulate in ischemic/hypoxic areas, worsening tissue injury by producing reactive oxygen species and other toxic mediators that compromise cellular metabolism and positively regulate a series of transcription factors, including HIF-1¿.Thus, the aim of this study is to identify the role of HIF-1¿ in macrophage metabolism after hypoxia/reoxygenation stimuli and in response to inflammatory stimuli. To this end, macrophages of the THP-1 cell line will be stimulated with 1¿g/mL LPS + 10 ng/mL IFN-¿, followed or not by a hypoxia protocol, in which the cells will be kept in an incubator with an environment of 0.3% O2 and 5% CO2 for 24 hours. Cell viability parameters, gene expression of HIF-1¿, IL-10, IL-1¿, TNF-¿ and PKM2 will be assessed, as well as lactate quantification. Our hypothesis is that HIF-1¿ modulates changes in macrophage metabolism during exposure to LPS+IFN-¿. (AU)