Phorbol ester markedly increases the sensitivity of intestinal epithelial cells to 1,25‐dihydroxyvitamin D₃

Abstract

We have used a clonal intestmal epithehal cell hne (IEC-18) to study the mechanism of action of 1,25_dihydroxyvitamm D, (1,25(OH)zD) in vitro. 1 ,25(OH)ZD (IO-' M) elevated by over IO-fold the mRNA levels for the cytochrome P450 component (P45Occ24) of the 1 ,25(OH)zD-24-hydroxylase. Increased P45Occ24 mRNA levels were detectable at 6 h and peaked at 36 h. Below a concentration of IO-' M, 1,25(OH),D had almost no effect. However, additton of phorbol ester for 2 h made the intestine responsive to 1,25(OH)ZD concentrations as low as lo-' M.

Differential Regulation of Vitamin D Receptor and Its Ligand in Human Monocyte-Derived Dendritic Cells

“…In these examples, the synthesis of 1␣25(OH) 2 D 3 may be controlled by the competing effects of another enzyme, 24(OH)ase, which inactivates 1␣25(OH) 2 D 3 . 24(OH)ase is itself induced by 1␣25(OH) 2 D 3 through a VDR-mediated mechanism (27,28). As shown in Fig.…”

Stat1-Vitamin D Receptor Interactions Antagonize 1,25-Dihydroxyvitamin D Transcriptional Activity and Enhance Stat1-Mediated Transcription

“…Since the mechanism for 1,25D-suppression of 1␣-hydroxylase gene transcription is poorly understood (37), we focused on the effects of IFN-␥ on 1,25D enhancement of its own catabolism. 1,25D induction of 24-hydroxylase expression is a typical 1,25D genomic action, mediated by ligandactivated vitamin D receptor (VDR) as a transcription factor (6,12). 1,25D binding to the VDR induces a conformational change in the VDR molecule that activates the VDR to translocate to the nucleus and heterodimerize with the retinoid X receptor (RXR).…”

Differential responsiveness of intestinal epithelial cells to 1,25-dihydroxyvitamin D3--role of protein kinase C

“…Thus, the activity of the 24-hydroxylase may regulate the action of 1,25(OH) 2 D in the intestine. 1,25(OH) 2 D markedly increases the mRNA levels of the cytochrome P450 component of the 24-hydroxylase (CYP24) in the intestine of intact animals (Armbrecht & Boltz 1991) and in intestinal cell lines (Armbrecht et al 1993, Koyama et al 1994.…”

“…1,25(OH) 2 D has been reported to increase CYP24 mRNA levels in both intestinal epithelial cells (IEC)-18 (Armbrecht et al 1993) and IEC-6 (Koyama et al 1994). These are non-transformed crypt-like cells isolated from the whole small intestine (IEC-6) (Quaroni et al 1979) or the ileum only (IEC-18) (Quaroni & Isselbacher 1981).…”