Counter-regulatory paracrine actions of FGF-23 and 1,25(OH)2 D in macrophages

FEBS Lett. 2016 Jan;590(1):53-67. doi: 10.1002/1873-3468.12040. Epub 2016 Jan 9.

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.

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