IL-36α and Lipopolysaccharide Cooperatively Induce Autophagy by Triggering Pro-Autophagic Biased Signaling
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 un...
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MDPI AG
2021-10-01
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| Online Access: | https://www.mdpi.com/2227-9059/9/11/1541 |
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| author | Zaid I. I. Al-Luhaibi Áron Dernovics György Seprényi Ferhan Ayaydin Zsolt Boldogkői Zoltán Veréb Klára Megyeri |
| author_facet | Zaid I. I. Al-Luhaibi Áron Dernovics György Seprényi Ferhan Ayaydin Zsolt Boldogkői Zoltán Veréb Klára Megyeri |
| author_sort | Zaid I. I. Al-Luhaibi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T05:41:21Z |
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| id | doaj.art-7bc9fda8b4fa41ce8d70ef8685d95dab |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T05:41:21Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-7bc9fda8b4fa41ce8d70ef8685d95dab2023-11-22T22:29:45ZengMDPI AGBiomedicines2227-90592021-10-01911154110.3390/biomedicines9111541IL-36α and Lipopolysaccharide Cooperatively Induce Autophagy by Triggering Pro-Autophagic Biased SignalingZaid I. I. Al-Luhaibi0Áron Dernovics1György Seprényi2Ferhan Ayaydin3Zsolt Boldogkői4Zoltán Veréb5Klára Megyeri6Department of Medical Microbiology, Albert Szent-Györgyi Medical School, University of Szeged, Dóm tér 10, H-6720 Szeged, HungaryDepartment of Medical Microbiology, Albert Szent-Györgyi Medical School, University of Szeged, Dóm tér 10, H-6720 Szeged, HungaryDepartment of Anatomy, Histology and Embryology, Albert Szent-Györgyi Medical School, University of Szeged, Kossuth L. sgt. 40, H-6724 Szeged, HungaryHungarian Centre of Excellence for Molecular Medicine (HCEMM) Nonprofit Ltd., Római krt. 21, H-6723 Szeged, HungaryDepartment of Medical Biology, Albert Szent-Györgyi Medical School, University of Szeged, Somogyi Béla u. 4, H-6720 Szeged, HungaryRegenerative Medicine and Cellular Pharmacology Laboratory, Albert Szent-Györgyi Medical School, University of Szeged, Korányi fasor 6, H-6720 Szeged, HungaryDepartment of Medical Microbiology, Albert Szent-Györgyi Medical School, University of Szeged, Dóm tér 10, H-6720 Szeged, HungaryAutophagy 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.https://www.mdpi.com/2227-9059/9/11/1541IL-36αLPSautophagyLC3BBeclin-1 |
| spellingShingle | Zaid I. I. Al-Luhaibi Áron Dernovics György Seprényi Ferhan Ayaydin Zsolt Boldogkői Zoltán Veréb Klára Megyeri IL-36α and Lipopolysaccharide Cooperatively Induce Autophagy by Triggering Pro-Autophagic Biased Signaling Biomedicines IL-36α LPS autophagy LC3B Beclin-1 |
| title | IL-36α and Lipopolysaccharide Cooperatively Induce Autophagy by Triggering Pro-Autophagic Biased Signaling |
| title_full | IL-36α and Lipopolysaccharide Cooperatively Induce Autophagy by Triggering Pro-Autophagic Biased Signaling |
| title_fullStr | IL-36α and Lipopolysaccharide Cooperatively Induce Autophagy by Triggering Pro-Autophagic Biased Signaling |
| title_full_unstemmed | IL-36α and Lipopolysaccharide Cooperatively Induce Autophagy by Triggering Pro-Autophagic Biased Signaling |
| title_short | IL-36α and Lipopolysaccharide Cooperatively Induce Autophagy by Triggering Pro-Autophagic Biased Signaling |
| title_sort | il 36α and lipopolysaccharide cooperatively induce autophagy by triggering pro autophagic biased signaling |
| topic | IL-36α LPS autophagy LC3B Beclin-1 |
| url | https://www.mdpi.com/2227-9059/9/11/1541 |
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