Nitric oxide (NO) produced at high concentrations by the inducible NO synthase is an important effector molecule involved in immune regulation and defense. The involvement of NO in the toxicity of cadmium (Cd) has been proposed. We have established that Cd inhibits the production of NO by recombinant IFN-gamma (rIFN-gamma) and lipopolysaccharide-stimulated mouse peritoneal macrophages. In the present study, we searched restoration drug against the inhibition of NO production by Cd in Oriental medicine. An aqueous extract of Taraxacum officinale (Compositae) (TOAE) restored the inhibition of NO production by mouse peritoneal macrophages pretreated with Cd in a dose-dependent manner. The effect of TOAE was mainly dependent on TOAE-induced tumor necrosis factor-alpha (TNF-alpha) secretion. These results suggest that the capacity of TOAE to restore NO production from interferon-gamma (IFN-gamma)-primed mouse peritoneal macrophages is the result of TOAE-induced TNF-alpha secretion.
SUMMARYWe have investigated the ability of an antisense immunoglobulin E (IgE) receptor a-subunit oligodeoxynucleotide (FceRIa ODN ) specifically to inhibit IgE-mediated allergic reactions in the mouse. Synthetic antisense FceRIa ODN dose-dependently inhibited passive cutaneous anaphylaxis and histamine release from the mouse peritoneal mast cells (MPMC ) activated by antidinitrophenyl (DNP) IgE. Northern blot analysis showed that the mast cells treated with antisense FceRIa ODN exhibited no detectable levels of -histidine decarboxylase mRNA after anti-DNP IgE stimulation, whereas the cells treated with sense FceRIa ODN possessed significant amounts of this mRNA. Examination of the elevation of cAMP levels in MPMC following the activation with anti-DNP IgE demonstrated a significant rise in activated cells, but not in the antisense FceRIa ODN-treated cells. Moreover, antisense FceRIa ODN had a significant inhibitory effect on anti-DNP IgE-induced tumour necrosis factor-a production. Our results demonstrated that antisense FceRIa ODN inhibited the IgE-mediated allergic reaction in vivo and in vitro.
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