Distinct role of FoxO1 in M-CSF- and GM-CSF-differentiated macrophages contributes LPS-mediated IL-10: implication in hyperglycemia. Issue 2 (24th November 2014)

• Record Type: Journal Article
• Authors: Chung, Sangwoon; Ranjan, Ravi; Lee, Yong Gyu; Park, Gye Young; Karpurapu, Manjula; Deng, Jing; Xiao, Lei; Kim, Ji Young; Unterman, Terry G; Christman, John W
• Is Part Of: Journal of leukocyte biology. Volume 97:Issue 2(2015)
• Page Start: 327
• Page End: 339
• Publication Date: 2014-11-24
• Subjects: monocyte -- metabolic stress -- M1-like -- M2-like -- inflammation; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.3A0514-251R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : A novel role for FoxO1 in regulating macrophage phenotypic polarization and therapeutic interventions for chronic inflammatory conditions. 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.