Pro-inflammatory polarization of macrophages is associated with reduced endoplasmic reticulum-mitochondria interaction

Autor(es)

Assis, Leandro Henrique de Paula ; Dorighello, Gabriel de Gabriel ; De Oliveira, Helena Coutinho Franco

• Tipo de documento: Artigo Científico
• Fonte: Biochemical and Biophysical Research Communications; v. 606, p. 7-pg., 2022-05-28.

Resumo

Macrophages play a role in host defense, tissue remodeling and inflammation. Different inflammatory stimuli drive macrophage phenotypes and responses. In this study we investigated the relationship between macrophages immune phenotype and mitochondrial bioenergetics, cell redox state and endoplasmic reticulum (ER)-mitochondria interaction. Bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN gamma) pro-inflammatory stimuli decreased oxidative metabolism (basal, phosphorylating and maximal conditions) and increased baseline glycolysis (117%) and glycolytic capacity (43%) in THP-1 macrophages. In contrast, interleukin-4 (IL4) and interleukin-13 (IL13) anti-inflammatory stimuli increased the oxygen consumption rates in baseline conditions (21%) and associated with ATP production (19%). LPS + IFN gamma stimuli reduced superoxide anion levels by accelerating its conversion into hydrogen peroxide (H2O2) while IL4+IL13 decreased H2O2 release rates. The source of these oxidants was extra-mitochondrial and associated with increased NOX2 and SOD1 gene expression. LPS + IFN gamma stimuli decreased ER-mitochondria contact sites as measured by IP3R1-VDAC1 interaction (34%) and markedly upregulated genes involved in mitochondrial fusion (9-10 fold, MFN1 and 2) and fission (similar to 7 fold, DRP1 and FIS1). Conversely, IL4+IL13 stimuli did not altered ER-mitochondria interactions nor MFN1 and 2 expression. Together, these results unveil ER-mitochondria interaction pattern as a novel feature of macrophage immunological, metabolic and redox profiles. (C) 2022 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 13/50615-1 - Laboratório de Biologia Celular e Molecular Multiusuários sediado no Instituto de Biologia da UNICAMP
• Beneficiário: Helena Coutinho Franco de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/17728-8 - Função e disfunção mitocondrial: implicações para o envelhecimento e doenças associadas
• Beneficiário: Aníbal Eugênio Vercesi
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/02903-9 - Papel da expressão de CETP no estado redox de macrófagos: possível relevância para inflamação e aterosclerose
• Beneficiário: Gabriel de Gabriel Taffarello Dorighello
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/03402-3 - Estudo da associação de membranas mitocondriais e de retículo endoplasmático em macrófagos no contexto de hipercolesterolemia: possível relevância para aterosclerose
• Beneficiário: Leandro Henrique de Paula Assis
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado