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Regulation of TNF-alpha release from bone marrow-derived macrophages by vitamin D.
- Source :
-
Journal of cellular biochemistry [J Cell Biochem] 1994 Aug; Vol. 55 (4), pp. 435-44. - Publication Year :
- 1994
-
Abstract
- The calcium-regulating hormone 1,25-dihydroxyvitamin D3[1,25(OH)2D3] is recognized as an immunomodulator 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-alpha (TNF-alpha) 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-alpha 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-alpha. BMDMs did not release measurable amounts of TNF-alpha without stimulation. Addition of endotoxin (LPS) to the cultures, resulted in a marked stimulation of TNF-alpha 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-gamma (IFN-gamma), yielded essentially similar results. +D and -D mice were injected with LPS and TNF-alpha levels in the serum were measured. A marked reduction (approximately fourfold) in the TNF-alpha 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-alpha synthesis. Our findings suggest that 1,25(OH)2D3 plays a role in the regulation of TNF-alpha secretion by mononuclear phagocytes.
- Subjects :
- Animals
Bone Marrow pathology
Cells, Cultured
Culture Media, Conditioned
Enzyme-Linked Immunosorbent Assay
Interferon-gamma pharmacology
Lipopolysaccharides pharmacology
Macrophages drug effects
Male
Mice
Mice, Inbred BALB C
Molecular Weight
Reference Values
Sensitivity and Specificity
Tumor Necrosis Factor-alpha isolation & purification
Bone Marrow Cells
Calcitriol pharmacology
Macrophages metabolism
Tumor Necrosis Factor-alpha biosynthesis
Vitamin D Deficiency metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0730-2312
- Volume :
- 55
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 7962175
- Full Text :
- https://doi.org/10.1002/jcb.240550404