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

• Published in: PloS one 2013-11, Vol.8 (11), p.e81785-e81785
• Main Authors: Lee, Jae-Kyung, Chung, Jaegwon, Kannarkat, George T, Tansey, Malú G
• Format: Article
• Language: English
• Subjects: Age; Animals; B cells; Bone marrow; Cell activation; Cell Line, Tumor; Chemotaxis; Chemotaxis, Leukocyte; Cytokines; Cytokines - biosynthesis; Cytotoxicity; Dopamine; Dopamine receptors; Enzyme-Linked Immunosorbent Assay; Female; G proteins; Genes; Genotype & phenotype; Guanosine triphosphatases; Homeostasis; Inflammation; Inflammation Mediators - metabolism; Interleukin 12; Interleukin 4; Kinases; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Macrophage Activation - physiology; Macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Male; Medicine; Metabolism; Mice; Mice, Knockout; Microglia; mRNA; Neuroblastoma; Neuroblastoma cells; NF-κB protein; Ovarian cancer; Peritoneum; Phagocytes; Phagocytosis; Phosphorylation; Physiology; Priming; Proteins; Real-Time Polymerase Chain Reaction; RGS Proteins - genetics; RGS Proteins - physiology; RNA; Schizophrenia; Signaling; Toxicity; Tumor necrosis factor; Tumor necrosis factor-TNF
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0081785

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.