Effect of 1,25-dihydroxyvitamin D3 on induction of scavenger receptor and differentiation of 12-O-tetradecanoylphorbol-13-acetate-treated THP-1 human monocyte like cells.

We investigated the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the expression of scavenger receptors in human monocytic cell line (THP-1 cells) treated for 24 h with 12-O-tetradecanoylphorbol-13-acetate (TPA) which induces their differentiation into macrophages. The capacity to degrade 125I-labeled acetyl low density lipoprotein (LDL) was developed in accordance with macrophage differentiation. The treatment with 10 nM 1,25(OH)2D3 for 72 h inhibited the degradation of acetyl LDL by THP-1 macrophages in a dose-dependent manner, suggesting that 1,25(OH)2D3 inhibits scavenging function in macrophages. In order to clarify the mechanism of its inhibitory effect on degradation of acetyl LDL, we performed the ligand binding assay using 125I-labeled acetyl LDL. Scatchard analysis revealed that 1,25(OH)2D3 decreased the number of scavenger receptors without changing the affinity for acetyl LDL. We next examined the effect of 1,25(OH)2D3 on the expression of scavenger receptor mRNA. The mRNA of type I scavenger receptor was first detected in THP-1 cells 4 days after the treatment with TPA, the mRNA level increased up to 6 days, and then decreased. The treatment with 1,25(OH)2D3 for 72 h dramatically decreased the mRNA levels after the acquisition of macrophage phenotypes as evidenced by nonspecific esterase staining. However, 1,25(OH)2D3 did not affect the activity of nonspecific esterase nor the induction of interleukin-1 beta mRNA by lipopolysaccharide in THP-1 macrophages. These findings suggest that 1,25(OH)2D3 exclusively decreases the expression of scavenger receptors in TPA-induced THP-1 macrophages without affecting the basic cellular functions as macrophages.