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enhances retinoic acid-mediated expression of
bone-type alkaline phosphatase in rat IEC-6 cells
1 Department of Nutrition, School of Medicine, University of Tokushima, Tokushima 770-8503, Japan; 2 Department of Internal Medicine, Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri 63110; and 3 Therapeutic Application Development Group, Otsuka Pharmaceutical Company, Tokyo 101-8535, Japan
We previously
showed that vitamin A upregulated the expression of bone-type alkaline
phosphatase (ALP) in fetal rat small intestine and rat intestinal IEC-6
cells. In this study, we examined interactions between retinoic
acid (RA) and several growth factors/cytokines on the isozyme
expression in IEC-6 cells. Epidermal growth factor and interleukins
(ILs)-2, -4, -5, and -6 completely blocked the RA-mediated increase in
ALP activity. In contrast, IL-1
markedly increased the activity,
protein, and mRNA of the bone-type ALP only when RA was present.
IL-1
and/or RA did not change the type 1 IL-1 receptor transcript
level, whereas IL-1
enhanced the RA-induced expressions of retinoic
acid receptor-
(RAR-
) and retinoid X receptor-
(RXR-
) mRNAs
and RA-mediated RXR response element binding. The synergism of IL-1
and RA on ALP activity was completely blocked by protein kinase C (PKC)
inhibitors. Our results suggest that IL-1
may modify the ALP isozyme
expression in small intestinal epithelial cells by stimulating
PKC-dependent, RAR-
- and/or RXR-
-mediated signaling pathways.
retinoic acid receptors; retinoid X receptors; protein kinase C; fetal rat small intestine; alkaline phosphatase isozymes
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