TNF-ALPHA REGULATES IL-4-INDUCED FC-EPSILON-RII CD23 GENE-EXPRESSION AND SOLUBLE FC-EPSILON-RII RELEASE BY HUMAN MONOCYTES/

We examined the regulatory effects of TNF-alpha on IL-4-induced gene e xpression of the low-affinity receptor for IgE (Fc epsilon RII/CD23) i n human monocytes and IL-4-induced soluble Fc epsilon RII (sFc epsilon RII) release from monocytes. IL-4-induced Fc epsilon RII expression o n the surface of monocytes was reduced by TNF-alpha as early as 1 day after culture and the effect of TNF-alpha increased with prolonged cul ture. The present analysis was designed to examine whether or not TNF- alpha could suppress IL-4-induced Fc epsilon RII mRNA expression and e nhanced IL-4-induced sFc epsilon RII release, The addition of TNF-alph a to monocyte cultures with IL-4 significantly reduced Fc epsilon RII expression on the surface of monocytes and significantly increased sFc epsilon RII release from monocytes. Over time, there was an inverse r elationship between the disappearance of cell surface Fc epsilon RII a nd the appearance of sFc epsilon RII in culture supernatants. Fc epsil on RII mRNA expression in monocytes cultured with IL-4 was not affecte d by TNF-alpha when examined at 6 h after cultivation. When the cells were cultured with TNF-alpha for more than 24 h, however, TNF-alpha do wn-regulated IL-4-induced Fc epsilon RII mRNA levels, This correlated with the kinetics of down-regulation of IL-4-induced Fc epsilon RII ex pression on the surface of monocytes by TNF-alpha, These results sugge st that TNF-alpha-dependent reduction of IL-4-induced Fc epsilon RII e xpression on the surface of monocytes resulted, at least in part, from the suppression of Fc epsilon RII mRNA expression and the enhancement of sFc epsilon RII release.