TNF-α regulates IL-4-induced FcεRII/CD23 gene expression and soluble FcεRII release by human monocytes

Abstract

We examined the regulatory effects of TNF-α on IL-4-induced gene expression of the low-affinity receptor for IgE (FcεRII/CD23) in human monocytes and IL-4-induced soluble FcεRII (sFcεRII) release from monocytes. IL-4-induced FcεRII expression on the surface of monocytes was reduced by TNF-α as early as 1 day after culture and the effect of TNF-α increased with prolonged culture. The present analysis was designed to examine whether or not TNF-α could suppress IL-4-induced FcεRII mRNA expression and enhanced IL-4-induced sFcεRII release. The addition of TNF-α to monocyte cultures with IL-4 significantly reduced FcεRII expression on the surface of monocytes and significantly increased sFcεRII release from monocytes. Over time, there was an inverse relationship between the disappearance of cell surface FcεRII and the appearance of sFcεRII in culture supernatants. FcεRII mRNA expression in monocytes cultured with IL-4 was not affected by TNF-α when examined at 6 h after cultivation. When the cells were cultured with TNF-α for more than 24 h, however, TNF-α down-regulated IL-4-induced FcεRII mRNA levels. This correlated with the kinetics of down-regulation of IL-4-induced FCεRII expression on the surface of monocytes by TNF-α. These results suggest that TNF-αdependent reduction of IL-4-;induced FcεRII expression on the surface of monocytes resulted, at least in part, from the suppression of FcεRII mRNA expression and the enhancement of sFcεRII release.