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

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, I L-1 beta markedly increased the activity, protein, and mRNA of the bone-typ e ALP only when RA was present. IL-1 beta and/or RA did not change the type 1 IL-1 receptor transcript level, whereas IL-1 beta enhanced the RA-induce d expressions of retinoic acid receptor-beta (RAR-beta) and retinoid X rece ptor-beta (RXR-beta) mRNAs and RA-mediated RXR response element binding. Th e synergism of IL-1 beta and RA on ALP activity was completely blocked by p rotein kinase C (PKC) inhibitors. Our results suggest that IL-1 beta may mo dify the ALP isozyme expression in small intestinal epithelial cells by sti mulating PKC-dependent, RAR-beta- and/or RXR-beta -mediated signaling pathw ays.