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.
Keywords:
1,25(OH)2D; FGF-23; Klotho; interferon gamma; lipopolysaccharide; macrophages.
© 2015 Federation of European Biochemical Societies.
Publication types
-
Comparative Study
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Arginase / antagonists & inhibitors
-
Arginase / chemistry
-
Arginase / genetics
-
Arginase / metabolism
-
Calcitriol / metabolism*
-
Cells, Cultured
-
Fibroblast Growth Factor-23
-
Fibroblast Growth Factors / antagonists & inhibitors
-
Fibroblast Growth Factors / genetics
-
Fibroblast Growth Factors / metabolism*
-
Gene Expression Regulation / drug effects
-
Genes, Reporter / drug effects
-
HEK293 Cells
-
Humans
-
Immunity, Innate / drug effects
-
Macrophage Activation / drug effects
-
Macrophages / cytology
-
Macrophages / drug effects
-
Macrophages / immunology
-
Macrophages / metabolism*
-
Mice
-
Paracrine Communication* / drug effects
-
Promoter Regions, Genetic / drug effects
-
Protein Kinase Inhibitors / pharmacology
-
Pyrimidines / pharmacology
-
RAW 264.7 Cells
-
Receptor, Fibroblast Growth Factor, Type 1 / agonists*
-
Receptor, Fibroblast Growth Factor, Type 1 / antagonists & inhibitors
-
Receptor, Fibroblast Growth Factor, Type 1 / metabolism
-
Receptors, Calcitriol / agonists*
-
Receptors, Calcitriol / metabolism
-
Recombinant Fusion Proteins / chemistry
-
Recombinant Fusion Proteins / metabolism
-
Recombinant Proteins / chemistry
-
Recombinant Proteins / metabolism
-
Signal Transduction* / drug effects
Substances
-
FGF23 protein, human
-
Fgf23 protein, mouse
-
PD 173074
-
Protein Kinase Inhibitors
-
Pyrimidines
-
Receptors, Calcitriol
-
Recombinant Fusion Proteins
-
Recombinant Proteins
-
Fibroblast Growth Factors
-
Fibroblast Growth Factor-23
-
Fgfr1 protein, mouse
-
Receptor, Fibroblast Growth Factor, Type 1
-
Arg1 protein, mouse
-
Arginase
-
Calcitriol