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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Autores principales:	Zaid I. I. Al-Luhaibi, Áron Dernovics, György Seprényi, Ferhan Ayaydin, Zsolt Boldogkői, Zoltán Veréb, Klára Megyeri
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	IL-36α LPS autophagy LC3B Beclin-1 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7bc9fda8b4fa41ce8d70ef8685d95dab
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spelling	oai:doaj.org-article:7bc9fda8b4fa41ce8d70ef8685d95dab2021-11-25T16:48:47ZIL-36α and Lipopolysaccharide Cooperatively Induce Autophagy by Triggering Pro-Autophagic Biased Signaling10.3390/biomedicines91115412227-9059https://doaj.org/article/7bc9fda8b4fa41ce8d70ef8685d95dab2021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1541https://doaj.org/toc/2227-9059Autophagy 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.Zaid I. I. Al-LuhaibiÁron DernovicsGyörgy SeprényiFerhan AyaydinZsolt BoldogkőiZoltán VerébKlára MegyeriMDPI AGarticleIL-36αLPSautophagyLC3BBeclin-1Biology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1541, p 1541 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	IL-36α LPS autophagy LC3B Beclin-1 Biology (General) QH301-705.5
spellingShingle	IL-36α LPS autophagy LC3B Beclin-1 Biology (General) QH301-705.5 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
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.
format	article
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
title	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_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_sort	il-36α and lipopolysaccharide cooperatively induce autophagy by triggering pro-autophagic biased signaling
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7bc9fda8b4fa41ce8d70ef8685d95dab
work_keys_str_mv	AT zaidiialluhaibi il36aandlipopolysaccharidecooperativelyinduceautophagybytriggeringproautophagicbiasedsignaling AT arondernovics il36aandlipopolysaccharidecooperativelyinduceautophagybytriggeringproautophagicbiasedsignaling AT gyorgyseprenyi il36aandlipopolysaccharidecooperativelyinduceautophagybytriggeringproautophagicbiasedsignaling AT ferhanayaydin il36aandlipopolysaccharidecooperativelyinduceautophagybytriggeringproautophagicbiasedsignaling AT zsoltboldogkoi il36aandlipopolysaccharidecooperativelyinduceautophagybytriggeringproautophagicbiasedsignaling AT zoltanvereb il36aandlipopolysaccharidecooperativelyinduceautophagybytriggeringproautophagicbiasedsignaling AT klaramegyeri il36aandlipopolysaccharidecooperativelyinduceautophagybytriggeringproautophagicbiasedsignaling
_version_	1718412964569022464

IL-36α and Lipopolysaccharide Cooperatively Induce Autophagy by Triggering Pro-Autophagic Biased Signaling

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