Resolving macrophage polarization through distinct Ca2+ entry channel that maintains intracellular signaling and mitochondrial bioenergetics

Summary: Transformation of naive macrophages into classically (M1) or alternatively (M2) activated macrophages regulates the inflammatory response. Here, we identified that distinct Ca2+ entry channels determine the IFNγ-induced M1 or IL-4-induced M2 transition. Naive or M2 macrophages exhibit a rob...

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Autores principales:	Viviane Nascimento Da Conceicao, Yuyang Sun, Karthik Ramachandran, Arun Chauhan, Amritha Raveendran, Manigandan Venkatesan, Bony DeKumar, Soumya Maity, Neelanjan Vishnu, George A. Kotsakis, Paul F. Worley, Donald L. Gill, Bibhuti B. Mishra, Muniswamy Madesh, Brij B. Singh
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Immune system Molecular biology Molecular network Science Q
Acceso en línea:	https://doaj.org/article/07366b1458be4b4bbeed13ff5fe16ed8
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spelling	oai:doaj.org-article:07366b1458be4b4bbeed13ff5fe16ed82021-11-20T05:10:09ZResolving macrophage polarization through distinct Ca2+ entry channel that maintains intracellular signaling and mitochondrial bioenergetics2589-004210.1016/j.isci.2021.103339https://doaj.org/article/07366b1458be4b4bbeed13ff5fe16ed82021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221013080https://doaj.org/toc/2589-0042Summary: Transformation of naive macrophages into classically (M1) or alternatively (M2) activated macrophages regulates the inflammatory response. Here, we identified that distinct Ca2+ entry channels determine the IFNγ-induced M1 or IL-4-induced M2 transition. Naive or M2 macrophages exhibit a robust Ca2+ entry that was dependent on Orai1 channels, whereas the M1 phenotype showed a non-selective TRPC1 current. Blockade of Ca2+ entry suppresses pNF-κB/pJNK/STAT1 or STAT6 signaling events and consequently lowers cytokine production that is essential for M1 or M2 functions. Of importance, LPS stimulation shifted M2 cells from Orai1 toward TRPC1-mediated Ca2+ entry and TRPC1−/− mice exhibited transcriptional changes that suppress pro-inflammatory cytokines. In contrast, Orai1−/− macrophages showed a decrease in anti-inflammatory cytokines and exhibited a suppression of mitochondrial oxygen consumption rate and inhibited mitochondrial shape transition specifically in the M2 cells. Finally, alterations in TRPC1 or Orai1 expression determine macrophage polarization suggesting a distinct role of Ca2+ channels in modulating macrophage transformation.Viviane Nascimento Da ConceicaoYuyang SunKarthik RamachandranArun ChauhanAmritha RaveendranManigandan VenkatesanBony DeKumarSoumya MaityNeelanjan VishnuGeorge A. KotsakisPaul F. WorleyDonald L. GillBibhuti B. MishraMuniswamy MadeshBrij B. SinghElsevierarticleImmune systemMolecular biologyMolecular networkScienceQENiScience, Vol 24, Iss 11, Pp 103339- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immune system Molecular biology Molecular network Science Q
spellingShingle	Immune system Molecular biology Molecular network Science Q Viviane Nascimento Da Conceicao Yuyang Sun Karthik Ramachandran Arun Chauhan Amritha Raveendran Manigandan Venkatesan Bony DeKumar Soumya Maity Neelanjan Vishnu George A. Kotsakis Paul F. Worley Donald L. Gill Bibhuti B. Mishra Muniswamy Madesh Brij B. Singh Resolving macrophage polarization through distinct Ca2+ entry channel that maintains intracellular signaling and mitochondrial bioenergetics
description	Summary: Transformation of naive macrophages into classically (M1) or alternatively (M2) activated macrophages regulates the inflammatory response. Here, we identified that distinct Ca2+ entry channels determine the IFNγ-induced M1 or IL-4-induced M2 transition. Naive or M2 macrophages exhibit a robust Ca2+ entry that was dependent on Orai1 channels, whereas the M1 phenotype showed a non-selective TRPC1 current. Blockade of Ca2+ entry suppresses pNF-κB/pJNK/STAT1 or STAT6 signaling events and consequently lowers cytokine production that is essential for M1 or M2 functions. Of importance, LPS stimulation shifted M2 cells from Orai1 toward TRPC1-mediated Ca2+ entry and TRPC1−/− mice exhibited transcriptional changes that suppress pro-inflammatory cytokines. In contrast, Orai1−/− macrophages showed a decrease in anti-inflammatory cytokines and exhibited a suppression of mitochondrial oxygen consumption rate and inhibited mitochondrial shape transition specifically in the M2 cells. Finally, alterations in TRPC1 or Orai1 expression determine macrophage polarization suggesting a distinct role of Ca2+ channels in modulating macrophage transformation.
format	article
author	Viviane Nascimento Da Conceicao Yuyang Sun Karthik Ramachandran Arun Chauhan Amritha Raveendran Manigandan Venkatesan Bony DeKumar Soumya Maity Neelanjan Vishnu George A. Kotsakis Paul F. Worley Donald L. Gill Bibhuti B. Mishra Muniswamy Madesh Brij B. Singh
author_facet	Viviane Nascimento Da Conceicao Yuyang Sun Karthik Ramachandran Arun Chauhan Amritha Raveendran Manigandan Venkatesan Bony DeKumar Soumya Maity Neelanjan Vishnu George A. Kotsakis Paul F. Worley Donald L. Gill Bibhuti B. Mishra Muniswamy Madesh Brij B. Singh
author_sort	Viviane Nascimento Da Conceicao
title	Resolving macrophage polarization through distinct Ca2+ entry channel that maintains intracellular signaling and mitochondrial bioenergetics
title_short	Resolving macrophage polarization through distinct Ca2+ entry channel that maintains intracellular signaling and mitochondrial bioenergetics
title_full	Resolving macrophage polarization through distinct Ca2+ entry channel that maintains intracellular signaling and mitochondrial bioenergetics
title_fullStr	Resolving macrophage polarization through distinct Ca2+ entry channel that maintains intracellular signaling and mitochondrial bioenergetics
title_full_unstemmed	Resolving macrophage polarization through distinct Ca2+ entry channel that maintains intracellular signaling and mitochondrial bioenergetics
title_sort	resolving macrophage polarization through distinct ca2+ entry channel that maintains intracellular signaling and mitochondrial bioenergetics
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/07366b1458be4b4bbeed13ff5fe16ed8
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Resolving macrophage polarization through distinct Ca2+ entry channel that maintains intracellular signaling and mitochondrial bioenergetics

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