Hypoxia shapes autophagy in LPS-activated dendritic cells
| Autor: | Antonella Naldini, Daniela Rossi, Irene Filippi, Sara Monaci, Fabio Carraro, Silvano Sozzani, Cristina Ulivieri, Giuseppe Marotta, Gaia Giuntini, Carlo Aldinucci |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Lipopolysaccharides
lcsh:Immunologic diseases. Allergy autophagy dendritic cell Immunology (macroautophagy) hypoxia hypoxia-inducible factor (HIF)-1α lipopolysaccharide (LPS) Lymphocyte Antigen 96 Autophagy-Related Proteins Ligands Immunofluorescence macroautophagy chemistry.chemical_compound Downregulation and upregulation medicine Humans Immunology and Allergy Cells Cultured Original Research medicine.diagnostic_test Autophagy Bafilomycin Dendritic Cells Dendritic cell Hypoxia (medical) Cell Hypoxia Cell biology Toll-Like Receptor 4 Blot chemistry TLR4 Cytokines medicine.symptom lcsh:RC581-607 Signal Transduction |
| Zdroj: | Frontiers in Immunology, Vol 11 (2020) Frontiers in Immunology |
| Popis: | During their lifespan, dendritic cells (DCs) are exposed to different pO2 levels that affect their differentiation and functions. Autophagy is one of the adaptive responses to hypoxia with important implications for cell survival. While the autophagic machinery in DCs was shown to impact signaling of TLRs, its regulation by the MD-2/TLR4 ligand LPS is still unclear. The aim of this study was to evaluate whether LPS can induce autophagy in DCs exposed to either aerobic or hypoxic conditions. Using human monocyte-derived DCs and the combination of immunofluorescence confocal analysis, measure of mitochondrial membrane potential, Western blotting, and RT-qPCR, we showed that the ability of LPS to modulate autophagy was strictly dependent upon pO2 levels. Indeed, LPS inhibited autophagy in aerobic conditions whereas the autophagic process was induced in a hypoxic environment. Under hypoxia, LPS treatment caused a significant increase of functional lysosomes, LC3B and Atg protein upregulation, and reduction of SQSTM1/p62 protein levels. This selective regulation was accompanied by activation of signalling pathways and expression of cytokines typically associated with DC survival. Bafilomycin A1 and chloroquine, which are recognized as autophagic inhibitors, confirmed the induction of autophagy by LPS under hypoxia and its impact on DC survival. In conclusion, our results show that autophagy represents one of the mechanisms by which the activation of the MD-2/TLR4 ligand LPS promotes DC survival under hypoxic conditions. |
| Databáze: | OpenAIRE |
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