Regulation of TNF‐α release from bone marrow–derived macrophages by vitamin D

Yousef Abu‐Amer, Zvi Bar‐Shavit

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The calcium‐regulating hormone 1,25‐dihydroxyvitamin D3[1,25(OH)2D3] is recognized as an immuno‐modulator affecting the activities of macrophages and lymphocytes. We have shown that macrophages harvested from vitamin D–deficient mice (–D MPs) exhibit impaired phagocytic and tumoricidal activities as compared with control cells (+D MPs), and that bone marrow–derived macrophage (BMDM) differentiation is modulated by 1,25(OH)2D3. The release of tumor necrosis factor–α (TNF‐α) by macrophages is considered a major mechanism by which these cells exert their tumoricidal function. This cytokine was also implicated in modulation of bone resorption. In the present study we examine the role of 1,25(OH)2D3 in TNF‐α synthesis and release. BMDMs were harvested from +D and −D mice, cultured in vitro, and their conditioned media were analyzed for the presence of TNF‐α. BMDMs did not release measurable amounts of TNF‐α without stimulation. Addition of endotoxin (LPS) to the cultures resulted in a marked stimulation of TNF‐α release. 1,25(OH)2D3 increased the stimulatory action of LPS, but failed to elicit a stimulatory effect in the absence of LPS. The use of another macrophage activator, interferon‐γ (IFN‐γ), yielded essentially similar results. +D and −D mice were injected with LPS and TNF‐α levels in the serum were measured. A marked reduction (∼ fourfold) in the TNF‐α levels was observed in the serum of −D mice as compared with +D mice. Western blot and immunoprecipitation analyses suggested that the main effect of 1,25(OH)2D3 is on TNF‐α synthesis. Our findings suggest that 1,25(OH)2D3 plays a role in the regulation of TNF‐α secretion by mononuclear phagocytes. © 1994 Wiley‐Liss, Inc.

Original languageEnglish
Pages (from-to)435-444
Number of pages10
JournalJournal of cellular biochemistry
Issue number4
StatePublished - Aug 1994


  • bone resorption
  • endotoxin
  • interferon γ
  • macrophage activation


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