科研之友
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摘要
During their development, human B lymphocytes migrate into various environments, each presenting important variations in their redox balance depending on oxygen availability. The modulation of the cells surroundings redox balance leads to the regulation of reactive oxygen species produced by the cell. These molecules are involved in the state of oxidation of the cytosol and affect many pathways involved in cell development, differentiation and protein secretion. B lymphocytes cultured in presence of interleukin (IL)-2, IL-4, IL-10 and under CD154 stimulation, present increases in their intracellular levels of ROS. However, when N-acetyl cysteine (NAC), an antioxidant, is added, STAT3 phosphorylation is decreased. In this study, we show that in activated human memory B cells, NAC inhibited STAT3 phosphorylation on tyrosine 705 but not on Serine 727. Moreover, higher concentrations of NAC decreased STAT3 synthesis. Two other antioxidants, a-tocopherol and Trolox, did not affect STAT3 phosphorylation. Furthermore, two kinases involved in STAT3 activation, known as JAK2 and JAK3, appeared down-regulated in presence of NAC. In parallel, 3 h after antioxidants incubation, we have observed a decrease in SOCS1 and SOCS3 protein levels, which seems time-related to antioxidant treatment. The decrease in the phosphorylation ofJAK2 and JAK3, earlier in the process, could explain the downregulation of STAT3 and offer a hypothesis on the mechanism of action of NAC antioxidant properties which were confirmed by a decrease in the level of S-glutathionylation of proteins. The reduced expression of SOCS1 and SOCS3 appears directly linked to the inhibition of this STAT3-regulated pathway. In summary, NAC appears as a potential regulator of the STAT3 pathway.
- 出版日期2014-11
