Signaling Through Purinergic Receptor P2Y<sub>2</sub> Enhances Macrophage IL-1β Production

The release of nucleotides during necrosis or apoptosis has been described to have both proinflammatory and anti-inflammatory effect on the surrounding cells. Here we describe how low concentrations of UTP and ATP applied during macrophage priming enhance IL-1β production when subsequently the NLRP3...

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Main Authors: Gonzalo de la Rosa, Ana I. Gómez, María C. Baños, Pablo Pelegrín
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/13/4686
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author Gonzalo de la Rosa
Ana I. Gómez
María C. Baños
Pablo Pelegrín
author_facet Gonzalo de la Rosa
Ana I. Gómez
María C. Baños
Pablo Pelegrín
author_sort Gonzalo de la Rosa
collection DOAJ
description The release of nucleotides during necrosis or apoptosis has been described to have both proinflammatory and anti-inflammatory effect on the surrounding cells. Here we describe how low concentrations of UTP and ATP applied during macrophage priming enhance IL-1β production when subsequently the NLRP3 inflammasome is activated in murine resident peritoneal macrophages. Deficiency or pharmacological inhibition of the purinergic receptor P2Y<sub>2</sub> reverted the increase of IL-1β release induced by nucleotides. IL-1β increase was found dependent on the expression of <i>Il1b</i> gene and probably involving JNK activity. On the contrary, nucleotides decreased the production of a different proinflammatory cytokines such as TNF-α. These results suggest that nucleotides could shape the response of macrophages to obtain a unique proinflammatory signature that might be relevant in unrevealing specific inflammatory conditions.
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spelling doaj.art-62c6ac1cc2ae4126b4ab425fe39d98b22023-11-20T05:30:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012113468610.3390/ijms21134686Signaling Through Purinergic Receptor P2Y<sub>2</sub> Enhances Macrophage IL-1β ProductionGonzalo de la Rosa0Ana I. Gómez1María C. Baños2Pablo Pelegrín3Unidad de Inflamación Molecular y Cirugía Experimental, Instituto Murciano de Investigación Biosanitaria IMIB-Arrixaca, Hospital Clínico Universitario Virgen de la Arrixaca, 30120 Murcia, SpainUnidad de Inflamación Molecular y Cirugía Experimental, Instituto Murciano de Investigación Biosanitaria IMIB-Arrixaca, Hospital Clínico Universitario Virgen de la Arrixaca, 30120 Murcia, SpainUnidad de Inflamación Molecular y Cirugía Experimental, Instituto Murciano de Investigación Biosanitaria IMIB-Arrixaca, Hospital Clínico Universitario Virgen de la Arrixaca, 30120 Murcia, SpainUnidad de Inflamación Molecular y Cirugía Experimental, Instituto Murciano de Investigación Biosanitaria IMIB-Arrixaca, Hospital Clínico Universitario Virgen de la Arrixaca, 30120 Murcia, SpainThe release of nucleotides during necrosis or apoptosis has been described to have both proinflammatory and anti-inflammatory effect on the surrounding cells. Here we describe how low concentrations of UTP and ATP applied during macrophage priming enhance IL-1β production when subsequently the NLRP3 inflammasome is activated in murine resident peritoneal macrophages. Deficiency or pharmacological inhibition of the purinergic receptor P2Y<sub>2</sub> reverted the increase of IL-1β release induced by nucleotides. IL-1β increase was found dependent on the expression of <i>Il1b</i> gene and probably involving JNK activity. On the contrary, nucleotides decreased the production of a different proinflammatory cytokines such as TNF-α. These results suggest that nucleotides could shape the response of macrophages to obtain a unique proinflammatory signature that might be relevant in unrevealing specific inflammatory conditions.https://www.mdpi.com/1422-0067/21/13/4686purinergic signalingmacrophagesinflammationcytokinesextracellular nucleotides
spellingShingle Gonzalo de la Rosa
Ana I. Gómez
María C. Baños
Pablo Pelegrín
Signaling Through Purinergic Receptor P2Y<sub>2</sub> Enhances Macrophage IL-1β Production
International Journal of Molecular Sciences
purinergic signaling
macrophages
inflammation
cytokines
extracellular nucleotides
title Signaling Through Purinergic Receptor P2Y<sub>2</sub> Enhances Macrophage IL-1β Production
title_full Signaling Through Purinergic Receptor P2Y<sub>2</sub> Enhances Macrophage IL-1β Production
title_fullStr Signaling Through Purinergic Receptor P2Y<sub>2</sub> Enhances Macrophage IL-1β Production
title_full_unstemmed Signaling Through Purinergic Receptor P2Y<sub>2</sub> Enhances Macrophage IL-1β Production
title_short Signaling Through Purinergic Receptor P2Y<sub>2</sub> Enhances Macrophage IL-1β Production
title_sort signaling through purinergic receptor p2y sub 2 sub enhances macrophage il 1β production
topic purinergic signaling
macrophages
inflammation
cytokines
extracellular nucleotides
url https://www.mdpi.com/1422-0067/21/13/4686
work_keys_str_mv AT gonzalodelarosa signalingthroughpurinergicreceptorp2ysub2subenhancesmacrophageil1bproduction
AT anaigomez signalingthroughpurinergicreceptorp2ysub2subenhancesmacrophageil1bproduction
AT mariacbanos signalingthroughpurinergicreceptorp2ysub2subenhancesmacrophageil1bproduction
AT pablopelegrin signalingthroughpurinergicreceptorp2ysub2subenhancesmacrophageil1bproduction