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Author Notes:

Correspondence: Jae-Kyung Lee; Email: jaekyung.lee@emory.edu or Malú G. Tansey; Email: malu.tansey@emory.edu

Author Contributions: Conceived and designed the experiments: JKL, JC, GTK and MGT.

Performed the experiments: JKL, JC and GTK.

Analyzed the data: JKL, JC and GTK.

Contributed reagents/materials/analysis tools: JKL and MGT.

Wrote the manuscript: JKL, JC, GTK and MGT.

Acknowledgments: We thank Jianjun Chang for animal colony maintenance and technical assistance and members of the Tansey lab for useful discussions.

Disclosures: Please note that Malú G. Tansey is a PLOS ONE Editorial Board Member.

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Research Funding:

This work was supported by a pilot grant to JKL from the Emory Parkinson's Disease Collaborative Environmental Research Center (5P01ES016731-04) and NIH/NINDS 5R01NS072467 grant to MGT.

Critical Role of Regulator G-Protein Signaling 10 (RGS10) in Modulating Macrophage M1/M2 Activation

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Journal Title:

PLoS ONE

Volume:

Volume 8, Number 11

Publisher:

, Pages e81785-e81785

Type of Work:

Article | Final Publisher PDF

Abstract:

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.

Copyright information:

© 2013 Lee et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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