Retinoic acid modulates IL-4 receptor alpha chain expression and signaling pathways in intestinal epithelial cells and macrophages (51.3)

Abstract

Abstract We have shown that all-trans retinoic acid (ATRA) increased mRNA expression of several IL-4-induced chemokines in explanted porcine alveolar macrophages. We now describe that ATRA modulated IL-4-induced signaling pathways in primary macrophages, and several macrophage and epithelial cell lines. ATRA increased epithelial cell mRNA and protein for the IL-4 receptor alpha chain (IL4RA), and IL-4 induced phosphorylation of STAT6 and expression of CLCA1 mRNA in vitro. In primary macrophages and several macrophage cell lines, ATRA-induced IL4RA mRNA and enhanced IL-4-induced expression of DHSR3, MRC1, PLAT, PTPN1, TGM2, and WARS mRNA and facilitated IL-4-inhibited expression of TLR2 and CYBB mRNA. However, ATRA blocked IL-4-induced expression of DHSR9, MAF, SEPP1 and STAT5A mRNA and counteracted IL-4 inhibited expression of BCL2L1, CCL2, NCF4, and PDGFB mRNA. These activities were largely shared by the RAR-a selective retinoid, Am580. ATRA variably affected the expression of a large number of other IL-4-induced mRNAs. These data indicated that ATRA and related retinoids can modulate Th2-related responses through mechanisms that utilize IL-4 and IL-4 receptor signaling pathways.