Posttranscriptional inhibition of interferon-gamma production by lead.

摘要: Lead (Pb) is known to preferentially suppress the activation and development of type-1 CD4+ helper T cell (Th1) responses, whereas it enhances type-2 (Th2) responses. The inhibition interferon-gamma (IFNgamma) production has been demonstrated in vitro with a Th1 clone DO11.10 ovalbumin-transgenic (OVA-tg) cells, vivo wild-type OVA-tg BALB/c mice; however, mechanisms responsible for Pb-induced downregulation IFNgamma have not reported. Here, we assessed modulation at mRNA protein levels. Pb did significantly affect expression by or activated splenocytes, as measured reverse transcriptase-polymerase chain reaction (RT-PCR), ribonuclease protection, real-time RT-PCR. However, lower amount supernatants lysates antigen-activated cells comparison stimulated controls, suggesting that amounts released into culture were due blockage secretion gave rise cytoplasmic accumulation IFNgamma. also was prevented addition zinc iron. enhance degradation IFNgamma, lactacystin, an effective blocker proteosomal proteolysis, prevent loss IFNgamma; additionally, accelerate after cycloheximide treatment. did, biosynthesis, investigated using 35S-incorporation pulse/chase experiments, although total synthesis, indicating selectively inhibits biosynthesis. Thus, appears interfere translation certain proteins, such IL-12 blocked Pb's preferential promotion Th2 but absence STAT6 skewing. may modulate unique regulatory pathways.