title: Counter-regulatory paracrine actions of FGF-23 and 1,25(OH)2 D in macrophages.
abstract: Mechanisms underlying the association between fibroblastic growth factor 23 (FGF-23) and inflammation are uncertain. We found that FGF-23 was markedly up-regulated in LPS/INF-γ-induced proinflammatory M1 macrophages and Hyp mouse-derived peritoneal macrophages, but not in IL-4-induced M2 anti-inflammatory macrophages. NF-КB and JAK/STAT1 pathways mediated the increased transcription of FGF-23 in response to M1 polarization. FGF-23 stimulated TNF-α, but not IL-6, expression in M0 macrophages and suppressed Arginase-1 expression in M2 macrophages through FGFR-mediated mechanisms. 1,25(OH)2 D stimulated Arginase-1 expression and inhibited FGF-23 stimulation of TNF-α. FGF-23 has proinflammatory paracrine functions and counter-regulatory actions to 1,25(OH)2 D on innate immune responses.
authors.affiliation: Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Linqiang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Yang
authors.affiliation: University of Alabama in Birmingham, AL, USA.
authors.forename: Gwendalyn
authors.initials: G
authors.lastname: King
authors.affiliation: Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Zhousheng
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Leigh Darryl
authors.initials: LD
authors.lastname: Quarles
mesh_terms: D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism*; D002478:Cells, Cultured; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D019899:Paracrine Communication / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000819:agonists* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; C115711:PD 173074; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D018167:Receptors, Calcitriol; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1; C544448:Arg1 protein, mouse; D001119:Arginase; D002117:Calcitriol
keywords: 1,25(OH)2D; FGF-23; Klotho; interferon gamma; lipopolysaccharide; macrophages