N-ACETYLCYSTEINE ATTENUATES TNF-ALPHA-DEPENDENT REDUCTION OF IL-4-INDUCED FC(EPSILON)RII EXPRESSION IN HUMAN MONOCYTES

We have previously shown that tumor necrosis factor-alpha (TNF-alpha) reduces interleukin-4 (IL-4)-induced Fc(epsilon)RII expression in huma n monocytes. It has been shown that TNF-alpha activates nuclear transc riptional factors through the generation of reactive oxygen intermedia tes (ROIs), and antioxidant N-acetylcysteine (NAC) inhibits TNF-alpha- induced activation of nuclear transcriptional factors. Therefore, we h ypothesized that TNF-alpha-dependent reduction of IL-4-induced Fc(epsi lon)RII expression in monocytes might be mediated through the ROIs-act ivated mechanism. In the present study, to test our hypothesis, we exa mined the effect of NAC on TNF-alpha-dependent reduction of IL-4-induc ed Fc(epsilon)RII expression in human monocytes. NAC attenuated TNF-al pha-dependent reduction of IL-4-induced Fc(epsilon)RII expression by a ttenuating TNF-alpha-dependent reduction of Fc(epsilon)RII mRNA expres sion. Similarly, the structurally unrelated antioxidant, pyrrolidine d ithiocarbamate (PDTC), also effectively attenuated this reduction. The se results indicate that an ROIs-activated and antioxidant-sensitive m echanism might be involved in TNF-alpha-dependent reduction of IL-4-in duced Fc(epsilon)RII expression in monocytes.