title: Critical role of regulator G-protein signaling 10 (RGS10) in modulating macrophage M1/M2 activation.
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.
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Lee
authors.forename: Jaegwon
authors.initials: J
authors.lastname: Chung
authors.forename: George T
authors.initials: GT
authors.lastname: Kannarkat
authors.forename: Malú G
authors.initials: MG
authors.lastname: Tansey
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis; D020710:RGS Proteins / Q000235:genetics / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D020710:RGS Proteins; C491068:Rgs10 protein, mouse