Cell studies examining the impact of vitamin D on inflammation.

<p>25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)₂), interferon gamma IFN-γ, interleukin 1β (IL1β), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin 12 (IL-12), interleukin 13 (IL-13), interleukin 15 (IL-15), interleukin 17 (IL-17), interleukin 21 (IL-21), monocyte chemotatic protein-1 (MCP-1), no change NC, peripheral blood mononuclear cells (PBMCs), tumor necrosis factor alpha (TNF- α).</p><p>^a Health status of participants unknown</p><p>^b Study conducted in participants with inadequate vitamin D status (serum 25(OH)D < 50 nM</p><p>Cell studies examining the impact of vitamin D on inflammation.</p

PRISMA flow diagram depicting the systematic study selection process.

<p>PBMC, peripheral blood mononuclear cells.</p

Overview of VDR-mediated regulation of cytokine transcription, production and secretion in immune cells.

<p>Interaction of VD3 and VDR leads to anti-inflammatory effects through negative regulation of NFκB and STAT1/5-mediated signalling. This results in decreased transcription of TNF-α, IL-6, MCP1 and IL-12β. VDR activation promotes increased intracellular glutathione levels that partially or fully attenuates excessive ROS production (ROS can activate pro-inflammatory NFκB signalling). Activated VDR regulates transcription of IL-2 and IL-10 through epigenetic and conformational changes in the promoter region of these genes. VDR association with the promoter region occurs in a cyclic fashion, which leads to initial gene suppression, followed by upregulation of IL-2 and IL-10 expression after 48 hours. Pro-inflammatory effects of VD3 were reported and suggested to be linked to increased IL-1β production possibly related to increased ERK1/2 phosphorylation and the transcription factor CEBPβ. The VDR is believed to modulate pro-inflammatory TLR expression both positively and negatively, but the mechanisms are unknown. Plasma membrane associated VDR may induce rapid effects through non-genomic pathways such as modulation of intracellular calcium levels, parathyroid hormone G-protein coupled or other second messenger systems. Non-genomic pathways may cooperate with genomic pathways to influence gene expression. CCAAT/enhancer binding protein beta (CEBPβ), extracellular signal-regulated kinase1/2 (ERK1/2), janus kinase (JAK), monocyte chemotatic protein1 (MCP-1), nuclear factor kappa light chain enhancer of activated B cells (NFκB), mitogen activated protein kinase (p38 MAPK), retinoid X receptor (RXR), reactive oxygen species (ROS), signal transducer and activator of transcription1/5 (STAT1/5), toll-like receptor-2/4 (TLR2/4), tumour necrosis factor alpha (TNF-α), vitamin D3 (VD3), vitamin D receptor (VDR).</p