Critical role of regulator G-protein signaling 10 (RGS10) in modulating macrophage M1/M2 activation.

Regulator of G protein signaling 10 (RGS10), a GTPase accelerating protein (GAP) for G alpha subunits, is a negative regulator of NF-κB in microglia. Here, we investigated the role of RGS10 in macrophages, a closely related myeloid-derived cell type. Features of classical versus alternative activati...

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Main Authors: Jae-Kyung Lee, Jaegwon Chung, George T Kannarkat, Malú G Tansey
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3836764?pdf=render
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author Jae-Kyung Lee
Jaegwon Chung
George T Kannarkat
Malú G Tansey
author_facet Jae-Kyung Lee
Jaegwon Chung
George T Kannarkat
Malú G Tansey
author_sort Jae-Kyung Lee
collection DOAJ
description Regulator of G protein signaling 10 (RGS10), a GTPase accelerating protein (GAP) for G alpha subunits, is a negative regulator of NF-κB in microglia. Here, we investigated the role of RGS10 in macrophages, a closely related myeloid-derived cell type. Features of classical versus alternative activation were assessed in Rgs10-/- peritoneal and bone marrow-derived macrophages upon LPS or IL-4 treatments, respectively. Our results showed that Rgs10-/- macrophages produced higher levels of pro-inflammatory cytokines including TNF, IL-1β and IL-12p70 in response to LPS treatment and exerted higher cytotoxicity on dopaminergic MN9D neuroblastoma cells. We also found that Rgs10-/- macrophages displayed a blunted M2 phenotype upon IL-4 priming. Specifically, Rgs10-/- macrophages displayed lower YM1 and Fizz1 mRNA levels as measured by QPCR compared to wild type macrophages upon IL-4 treatment and this response was not attributable to differences in IL-4 receptor expression. Importantly, phagocytic activities of Rgs10-/- macrophages were blunted in response to IL-4 priming and/or LPS treatments. However, there was no difference in chemotaxis between Rgs10-/- and WT macrophages. Our data indicate that Rgs10-/- macrophages displayed dysregulated M1 responses along with blunted M2 alternative activation responses, suggesting that RGS10 plays an important role in determining macrophage activation responses.
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spelling doaj.art-ea99784166514d88945257448f8114bf2022-12-21T18:21:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e8178510.1371/journal.pone.0081785Critical role of regulator G-protein signaling 10 (RGS10) in modulating macrophage M1/M2 activation.Jae-Kyung LeeJaegwon ChungGeorge T KannarkatMalú G TanseyRegulator of G protein signaling 10 (RGS10), a GTPase accelerating protein (GAP) for G alpha subunits, is a negative regulator of NF-κB in microglia. Here, we investigated the role of RGS10 in macrophages, a closely related myeloid-derived cell type. Features of classical versus alternative activation were assessed in Rgs10-/- peritoneal and bone marrow-derived macrophages upon LPS or IL-4 treatments, respectively. Our results showed that Rgs10-/- macrophages produced higher levels of pro-inflammatory cytokines including TNF, IL-1β and IL-12p70 in response to LPS treatment and exerted higher cytotoxicity on dopaminergic MN9D neuroblastoma cells. We also found that Rgs10-/- macrophages displayed a blunted M2 phenotype upon IL-4 priming. Specifically, Rgs10-/- macrophages displayed lower YM1 and Fizz1 mRNA levels as measured by QPCR compared to wild type macrophages upon IL-4 treatment and this response was not attributable to differences in IL-4 receptor expression. Importantly, phagocytic activities of Rgs10-/- macrophages were blunted in response to IL-4 priming and/or LPS treatments. However, there was no difference in chemotaxis between Rgs10-/- and WT macrophages. Our data indicate that Rgs10-/- macrophages displayed dysregulated M1 responses along with blunted M2 alternative activation responses, suggesting that RGS10 plays an important role in determining macrophage activation responses.http://europepmc.org/articles/PMC3836764?pdf=render
spellingShingle Jae-Kyung Lee
Jaegwon Chung
George T Kannarkat
Malú G Tansey
Critical role of regulator G-protein signaling 10 (RGS10) in modulating macrophage M1/M2 activation.
PLoS ONE
title Critical role of regulator G-protein signaling 10 (RGS10) in modulating macrophage M1/M2 activation.
title_full Critical role of regulator G-protein signaling 10 (RGS10) in modulating macrophage M1/M2 activation.
title_fullStr Critical role of regulator G-protein signaling 10 (RGS10) in modulating macrophage M1/M2 activation.
title_full_unstemmed Critical role of regulator G-protein signaling 10 (RGS10) in modulating macrophage M1/M2 activation.
title_short Critical role of regulator G-protein signaling 10 (RGS10) in modulating macrophage M1/M2 activation.
title_sort critical role of regulator g protein signaling 10 rgs10 in modulating macrophage m1 m2 activation
url http://europepmc.org/articles/PMC3836764?pdf=render
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