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

Interleukin-1 b enhances retinoic acid-mediated expression of bone-type alkaline phosphatase in rat IEC-6 cells. Am J Physiol Gastrointest Liver Physiol 280: G510–G517, 2001.—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 b markedly increased the activity, protein, and mRNA of the bone-type ALP only when RA was present. IL-1 b and/or RA did not change the type 1 IL-1 receptor transcript level, whereas IL-1 b enhanced the RA-induced expressions of retinoic acid receptor- b (RAR- b ) and retinoid X receptor- b (RXR- b ) mRNAs and RA-mediated RXR response element binding. The synergism of IL-1 b and RA on ALP activity was completely blocked by protein kinase C (PKC) inhibitors. Our results suggest that IL-1 b may modify the ALP isozyme expression in small intestinal epithelial cells by stimulating PKC-dependent, RAR- b - and/or RXR- b mediated signaling pathways.