Vitamin D3 inhibits proinflammatory cytokines and nitric oxide production by the EOC13 microglial cell line

Abstract

In recent years, a neuroimmunomodulatory role for 1,25-dihydroxyvitamine D(3) [1,25(OH)(2)D(3)] has emerged. Microglial cells present a potential target for the effects of this hormone in the brain. This study focuses on the effect of 1,25(OH)(2)D(3) on the expression and production of inflammatory cytokines and nitric oxide (NO) by the EOC13 microglial cell line. The presence of the vitamin D3 receptor in microglia was demonstrated by RT-PCR. 1,25(OH)(2)D(3) inhibited the production of tumor necrosis factor-alpha, interleukin-6, and NO by stimulated microglia in a concentration-related fashion. The production of transforming growth factor-beta1 (TGF-beta1), an anti-inflammatory cytokine, was not modified in the presence of 1,25(OH)(2)D(3), indicating that the effects of 1,25(OH)(2)D(3) may not involve TGF-beta1 regulation. These results show that 1,25(OH)(2)D(3) has direct anti-inflammatory properties on microglia. It further supports the hypothesis that 1,25(OH)(2)D(3) could be involved in the maintenance of the brain homeostasis and may have a therapeutic potential in inflammatory pathologies of the central nervous system.

Reconsidering the connection between vitamin D levels and age-related macular degeneration

“…Several studies have reported that vitamin D decreases the proliferation of T-helper cells, 23 T-cytotoxic cells and natural killer cells 24 and enhances T-suppressor cell activity. 31 Other studies have reported that vitamin D also decreases the production of proinflammatory agents, such as IL-2, 25,26 IL-8, 27 IL-6 28 and IL-12. 29 One recent study demonstrated that vitamin D intake reduces C-reactive protein, a marker of systemic inflammation.…”

“…[11][12][13][14]16 Evidence of inflammatory cell involvement in the later stages of AMD includes the presence of multinucleated giant cells and leukocytes in the choroid of AMD eyes 15 and in excised choroidal neovascularization. 20,22 A number of in vitro and in vivo studies have suggested an anti-inflammatory role for vitamin D. 23,24 It was also shown that vitamin D reduces the proliferation of cells of the immune system, [25][26][27][28][29] and that there is an inverse relationship between vitamin D levels and several chronic conditions associated with inflammation. [30][31][32][33] Owing to the potential causative role of inflammation in AMD development and progression, it is possible that vitamin D may protect against the occurrence and progression of AMD by virtue of its anti-inflammatory properties.…”

Immune-Glutamatergic Dysfunction as a Central Mechanism of the Autism Spectrum Disorders

“…Interestingly, it is known that microglia not only contain VDR but also can manufacture 1,25 dihydroxyvitamin D3 when activated [172,173]. Studies have also shown that during activation the number of VDR are up-regulated within the microglia.…”

The role of adult vitamin D deficiency in cognition and brain function in mice

“…Within the CNS, vitamin D exerts immunomodulatory effects directly on infiltrating macrophages and parenchymal microglia (Nataf et al, 1996). Treatment of microglia in vitro with vitamin D inhibits the production of tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), and NO by activated microglia, which suggests an anti-inflammatory role for vitamin D within the brain (Lefebvre d'Hellencourt et al, 2003). Vitamin D has been shown to downregulate the expression of inducible nitric oxide synthesis (iNOS) (Garcion et al, 1998) and to regulate the expression of gamma glutamyl transpeptidase (Garcion et al, 1999), an enzyme important in the glutathione pathway; these findings suggest that vitamin D has an important role in antioxidant metabolism.…”