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IL-36α and Lipopolysaccharide Cooperatively Induce Autophagy by Triggering Pro-Autophagic Biased Signaling
- Source :
- Biomedicines, Volume 9, Issue 11, Biomedicines, Vol 9, Iss 1541, p 1541 (2021)
- Publication Year :
- 2021
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2021.
-
Abstract
- Autophagy is an intracellular catabolic process that controls infections both directly and indirectly via its multifaceted effects on the innate and adaptive immune responses. It has been reported that LPS stimulates this cellular process, whereas the effect of IL-36α on autophagy remains largely unknown. We therefore investigated how IL-36α modulates the endogenous and LPS-induced autophagy in THP-1 cells. The levels of LC3B-II and autophagic flux were determined by Western blotting. The intracellular localization of LC3B was measured by immunofluorescence assay. The activation levels of signaling pathways implicated in autophagy regulation were evaluated by using a phosphokinase array. Our results showed that combined IL-36α and LPS treatment cooperatively increased the levels of LC3B-II and Beclin-1, stimulated the autophagic flux, facilitated intracellular redistribution of LC3B, and increased the average number of autophagosomes per cell. The IL36α/LPS combined treatment increased phosphorylation of STAT5a/b, had minimal effect on the Akt/PRAS40/mTOR pathway, and reduced the levels of phospho-Yes, phospho-FAK, and phospho-WNK1. Thus, this cytokine/PAMP combination triggers pro-autophagic biased signaling by several mechanisms and thus cooperatively stimulates the autophagic cascade. An increased autophagic activity of innate immune cells simultaneously exposed to IL-36α and LPS may play an important role in the pathogenesis of Gram-negative bacterial infections.
- Subjects :
- autophagy
LPS
QH301-705.5
medicine.medical_treatment
Medicine (miscellaneous)
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
medicine
LC3B
Biology (General)
Protein kinase B
PI3K/AKT/mTOR pathway
030304 developmental biology
IL-36α
0303 health sciences
Innate immune system
Chemistry
Autophagy
Cell biology
Cytokine
Phosphorylation
Beclin-1
Signal transduction
Intracellular
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 22279059
- Database :
- OpenAIRE
- Journal :
- Biomedicines
- Accession number :
- edsair.doi.dedup.....3db750f1746f81e234f494f266086ac9
- Full Text :
- https://doi.org/10.3390/biomedicines9111541