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

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--induced proinflammatory M1 macrophages and Hyp mouse-derived peritoneal macrophages, but not in IL-4-induced M2 anti-inflammatory macrophages. NF-?B and JAK/STAT1 pathways mediated the increased transcription of FGF-23 in response to M1 polarization. FGF-23 stimulated TNF-, 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-. FGF-23 has proinflammatory paracrine functions and counter-regulatory actions to 1,25(OH)(2)D on innate immune responses.