T cell IFN-γ suppression following alcohol and burn injury is independent of miRNA155.

T cell IFN-γ suppression following alcohol and burn injury is independent of miRNA155.
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DOI:
10.1371/journal.pone.0105314
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Choudhry MA
Choudhry MA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li X;Rendon JL;Choudhry MA

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MiRNA155参与了T细胞的正常功能及其向Th1亚型的分化。我们已经证明,急性酒精中毒合并烧伤会抑制T细胞干扰素-γ的释放。在这里,我们研究了干扰素-γ的降低是否由于酒精和烧伤后T细胞中miRNA155和转录因子NFAT、Tbx21、Jun和Fos表达的改变所致。小鼠在∼12.5%总体表面积、假手术或烧伤前4小时给予乙醇(∼3g/kg),伤后1天处死。取脾T细胞,加入抗CD3抗体(2µg/ml),加入或不加入rIL-12(10 ng/ml)或PMA(10 ng/ml)+离子霉素(50 ng/ml)培养48小时。我们观察到酒精和烧伤后T细胞经抗CD3抗体培养后,miRNA155、NFAT、Tbx21、Jun和Fos的表达以及干扰素-γ的释放均显著低于假手术组。T细胞与rIL-12共同作用可阻止干扰素-γ、NFAT、Tbx21、Jun和Fos的下降,但不能阻止miRNA155的下降。相反,PMA和离子霉素联合处理可使NFAT的表达正常化。但不能阻止干扰素-γ、Tbx21、Jun、Fos和miRNA155的降低。最后,在miRNA155-/-小鼠身上获得的结果显示,与野生型小鼠相比,T细胞干扰素-γ的释放或核因子的表达没有任何变化。综上所述,这些发现表明,尽管酒精和烧伤会降低miRNA155的表达,但在这些条件下,miRNA155可能与干扰素-γ的减少无关。
miRNA155 has been implicated in normal T cell function and their differentiations into the Th1 subtype. We have shown that acute alcohol (ethanol) intoxication combined with burn injury suppresses T cell IFN-γ release. Herein, we examined whether the decrease in IFN-γ is resulted from altered expression of miRNA155 and transcription factors -NFAT, Tbx21, Jun and Fos - in T cells following ethanol and burn injury. Mice received ethanol (∼3 g/Kg) 4 hours prior to ∼12.5% total body surface area sham or burn injury and were sacrificed one day after injury. Splenic T cells were harvested and cultured with anti-CD3 (2 µg/ml) in the presence or absence of rIL-12 (10 ng/ml) or PMA (10 ng/ml) plus ionomycin (50 ng/ml) for 48 hours. We observed a significant decrease in miRNA155, NFAT, Tbx21, Jun and Fos expression as well as IFN-γ release in T cells cultured with anti-CD3 following ethanol and burn injury compared with shams. The co-treatment of T cells with rIL-12 prevented the decrease in IFN-γ and NFAT, Tbx21, Jun and Fos, but not miRNA155. In contrast, the co-treatment with PMA plus ionomycin normalized the expression of NFAT. It did not prevent the decrease in IFN-γ, Tbx21, Jun, Fos and miRNA155. Finally, results obtained in miRNA155-/- mice did not show any change in T cell release of IFN-γ or expression of nuclear factors compared to wildtype mice. Together, these findings suggest that while ethanol and burn injury decreases the expression of miRNA155, it may not be involved in decreased IFN-γ under those conditions.
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