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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Public Library of Science (PLoS)
2013-01-01
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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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language | English |
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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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