| Full text | |
| Author(s): |
Assis, Leandro Henrique de Paula
;
Dorighello, Gabriel de Gabriel
;
De Oliveira, Helena Coutinho Franco
Total Authors: 3
|
| Document type: | Journal article |
| Source: | Biochemical and Biophysical Research Communications; v. 606, p. 7-pg., 2022-05-28. |
| Abstract | |
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) | |
| FAPESP's process: | 13/50615-1 - Cellular and molecular biology facility at the Biology Institute - UNICAMP |
| Grantee: | Helena Coutinho Franco de Oliveira |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 17/17728-8 - Mitochondrial function and dysfunction: implications for aging and associated diseases |
| Grantee: | Aníbal Eugênio Vercesi |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 17/02903-9 - Role of CETP expression in the macrophage redox state: possible consequences to inflammation and atherosclerosis |
| Grantee: | Gabriel de Gabriel Taffarello Dorighello |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 17/03402-3 - Study of the association of mitochondrial and endoplasmic reticulum membranes in macrophages in the context of hypercholesterolemia: possible relevance for atherosclerosis |
| Grantee: | Leandro Henrique de Paula Assis |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |