Beurton F, Gueret G, Horisberger M, Cheron G, Cresteil T
INSERM U75, Université René Descartes, 75730 Paris Cedex 15, France.
Int J Mol Med. 1999 Jan;3(1):33-9. doi: 10.3892/ijmm.3.1.33.
The expression of cytochrome P4502C has been shown to be upregulated in sudden infant death syndrome (SIDS) and could be linked to viral infection through the release of interferon alpha and interleukins. MxA is a reliable marker of IFNalpha release and its level was significantly enhanced in SIDS reflecting the release of IFNalpha in response to viral infection. Similarly, the concentration of Fas protein was increased in SIDS (2.6x control) and indicated a stimulation of the Fas gene expression. Accumulation of MxA and Fas proteins were visible in liver and to a lesser extent in lung and kidney. The amount of RNA encoding CYP2C9 (4.4x control), 2C8 (2.5x) and 2C18 (2.3x) was markedly higher in SIDS than in age-matched children and would suggest a transcriptional activation of CYP2C gene expression. Finally, CYP2C genes were shown to be adjacent to two IFN-inducible genes (IFI54 and IFI56) on chromosome 10. We conclude that in SIDS a viral infection leads to the release of IFNalpha which could activate a battery of IFN-inducible genes. This might modify the chromatin structure and facilitate the accessibility to promoter/regulatory sequences of CYP2C and Fas genes close to IFN-inducible gene on chromosome 10.
细胞色素P4502C的表达已被证实在婴儿猝死综合征（SIDS）中上调，并且可能通过α干扰素和白细胞介素的释放与病毒感染相关联。MxA是α干扰素释放的可靠标志物，其水平在SIDS中显著升高，反映了对病毒感染的α干扰素释放。同样，Fas蛋白的浓度在SIDS中增加（为对照的2.6倍），表明Fas基因表达受到刺激。MxA和Fas蛋白在肝脏中可见积累，在肺和肾脏中积累程度较轻。编码CYP2C9（为对照的4.4倍）、2C8（2.5倍）和2C18（2.3倍）的RNA量在SIDS中明显高于年龄匹配的儿童，这表明CYP2C基因表达存在转录激活。最后，CYP2C基因被证明与10号染色体上的两个干扰素诱导基因（IFI54和IFI56）相邻。我们得出结论，在SIDS中，病毒感染导致α干扰素释放，这可能会激活一系列干扰素诱导基因。这可能会改变染色质结构，并促进对10号染色体上靠近干扰素诱导基因的CYP2C和Fas基因启动子/调控序列的可及性。
