Priming Effect of Vitamin D₃ Analog on Human Monocytic Cells in Response to Microbe-Related Ligands, Especially NOD2 Agonistic Muramyldipeptide

Abstract

Activated vitamin D_3, 1α,25-dihydroxyvitamin D_3, exhibits various ­biological functions, including immunomodulating activities. Human monocytic THP-1 cells were primed with a vitamin D₃ analog, OCT, followed by stimulation with various Toll-like receptor (TLR), NOD1 and NOD2 ligands. The primed cells produced higher IL-8 than non-primed cells upon stimulation with the ligands. NOD2-agonistic muramyldipeptide (MDP) was the highest inducer of IL-8 production in the primed cells, and IL-8 production increased until 72 h-priming with OCT. OCT up-regulated the expression of NOD2 and the primed cells exhibited higher activation of p38, JNK and ERK in the MAPK pathway, IκBα in the NF-kB pathway, and TAK1 upstream in both pathways than non-primed cells. Analysis using inhibitors indicated that activation of the above signal molecules is required for the priming activity.