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Am J Physiol Gastrointest Liver Physiol 280: G510-G517, 2001;
0193-1857/01 $5.00
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Vol. 280, Issue 3, G510-G517, March 2001

Interleukin-1beta enhances retinoic acid-mediated expression of bone-type alkaline phosphatase in rat IEC-6 cells

Takeshi Nikawa1, Madoka Ikemoto1, Kaori Tokuoka1, Shigetada Teshima1, David H. Alpers2, Yoshihiro Masui3, Kyoichi Kishi1, and Kazuhito Rokutan1

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-1beta markedly increased the activity, protein, and mRNA of the bone-type ALP only when RA was present. IL-1beta and/or RA did not change the type 1 IL-1 receptor transcript level, whereas IL-1beta enhanced the RA-induced expressions of retinoic acid receptor-beta (RAR-beta ) and retinoid X receptor-beta (RXR-beta ) mRNAs and RA-mediated RXR response element binding. The synergism of IL-1beta and RA on ALP activity was completely blocked by protein kinase C (PKC) inhibitors. Our results suggest that IL-1beta may modify the ALP isozyme expression in small intestinal epithelial cells by stimulating PKC-dependent, RAR-beta - and/or RXR-beta -mediated signaling pathways.

retinoic acid receptors; retinoid X receptors; protein kinase C; fetal rat small intestine; alkaline phosphatase isozymes


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Am. J. Physiol. Gastrointest. Liver Physiol.Home page
T. Harada, I. Koyama, T. Kasahara, D. H. Alpers, and T. Komoda
Heat shock induces intestinal-type alkaline phosphatase in rat IEC-18 cells
Am J Physiol Gastrointest Liver Physiol, February 1, 2003; 284(2): G255 - G262.
[Abstract] [Full Text] [PDF]




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