title: Distinct role of FoxO1 in M-CSF- and GM-CSF-differentiated macrophages contributes LPS-mediated IL-10: implication in hyperglycemia.
abstract: Macrophages are a heterogeneous population of immune cells that are essential for the initiation and containment inflammation. There are 2 well-established populations of inflammatory macrophages: classically activated M1 and alternatively activated M2 macrophages. The FoxO family of transcription factors plays key roles in a number of cellular processes, including cell growth, metabolism, survival, and inflammation. In this study, we determined whether the expression of FoxO1 contributes polarization of macrophages toward the M2-like phenotype by enhancing IL-10 cytokine expression. We identified that FoxO1 is highly expressed in M-CSF-derived (M2-like) macrophage subsets, and this M2-like macrophages showed a preferential FoxO1 enrichment on the IL-10 promoter but not in GM-CSF-derived (M1-like) macrophages during classic activation by LPS treatment, which suggests that FoxO1 enhances IL-10 by binding directly to the IL-10 promoter, especially in BMMs. In addition, our data show that macrophages in the setting of hyperglycemia contribute to the macrophage-inflammatory phenotype through attenuation of the contribution of FoxO1 to activate IL-10 expression. Our data identify a novel role for FoxO1 in regulating IL-10 secretion during classic activation and highlight the potential for therapeutic interventions for chronic inflammatory conditions, such as atherosclerosis, diabetes, inflammatory bowel disease, and arthritis.
authors.affiliation: *Division of Pulmonary, Allergy, Critical Care, and Sleep, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA; Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois, Chicago, Illinois, USA; and Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA.
authors.forename: Sangwoon
authors.initials: S
authors.lastname: Chung
authors.affiliation: *Division of Pulmonary, Allergy, Critical Care, and Sleep, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA; Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois, Chicago, Illinois, USA; and Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Ranjan
authors.affiliation: *Division of Pulmonary, Allergy, Critical Care, and Sleep, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA; Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois, Chicago, Illinois, USA; and Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA.
authors.forename: Yong Gyu
authors.initials: YG
authors.lastname: Lee
authors.affiliation: *Division of Pulmonary, Allergy, Critical Care, and Sleep, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA; Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois, Chicago, Illinois, USA; and Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA.
authors.forename: Gye Young
authors.initials: GY
authors.lastname: Park
authors.affiliation: *Division of Pulmonary, Allergy, Critical Care, and Sleep, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA; Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois, Chicago, Illinois, USA; and Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA.
authors.forename: Manjula
authors.initials: M
authors.lastname: Karpurapu
authors.affiliation: *Division of Pulmonary, Allergy, Critical Care, and Sleep, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA; Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois, Chicago, Illinois, USA; and Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Deng
authors.affiliation: *Division of Pulmonary, Allergy, Critical Care, and Sleep, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA; Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois, Chicago, Illinois, USA; and Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Xiao
authors.affiliation: *Division of Pulmonary, Allergy, Critical Care, and Sleep, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA; Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois, Chicago, Illinois, USA; and Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: *Division of Pulmonary, Allergy, Critical Care, and Sleep, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA; Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois, Chicago, Illinois, USA; and Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA.
authors.forename: Terry G
authors.initials: TG
authors.lastname: Unterman
authors.affiliation: *Division of Pulmonary, Allergy, Critical Care, and Sleep, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA; Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois, Chicago, Illinois, USA; and Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, USA John.Christman@osumc.edu.
authors.forename: John W
authors.initials: JW
authors.lastname: Christman
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; C508609:IL10 protein, human; C556062:IL10 protein, mouse; D008070:Lipopolysaccharides; D016753:Interleukin-10; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: M1-like; M2-like; inflammation; metabolic stress; monocyte