Differential responses of normal human melanocytes to intra- and extracellular dsRNA.
Differential responses of normal human melanocytes to intra- and extracellular dsRNA.
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DOI：
10.1089/dna.2014.2711
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发表时间：
2015-06
影响因子：
3.1
通讯作者：
Suiquan Wang;Dongyin Liu;R. Jin;Yiping Zhu;A. Xu
中科院分区：
文献类型：
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作者：
Suiquan Wang;Dongyin Liu;R. Jin;Yiping Zhu;A. Xu
病毒因素参与了白癜风的发病机制。为了阐明病毒双链RNA（dsRNA）对黑素细胞的影响并探讨其潜在机制，用合成的病毒dsRNA类似物poly（I：C）处理原代培养的正常人黑素细胞。结果表明，poly（I：C）-在转染到黑素细胞中时触发凋亡，而胞外poly（I：C）没有这种作用。细胞内poly（I：C）诱导的黑素细胞死亡被RIG-I或MDA 5 siRNA降低，但不被TLR 3 siRNA降低。细胞内和细胞外poly（I：C）均诱导IFNB、TNF、IL 6和IL 8的表达。然而，细胞外poly（I：C）表现出比细胞内poly（I：C）弱得多的细胞因子基因的诱导能力。进一步的分析表明，TBK 1，IRF 3，IRF 7和TAK 1的磷酸化是由细胞内或细胞外poly（I：C）差异诱导的。NFκB抑制剂Bay 11-7082可降低poly（I：C）对所有细胞因子的诱导，提示NFκB在此过程中的普遍作用。Poly（I：C）处理也诱导黑素细胞中p38和JNK的磷酸化。JNK和p38抑制剂都显示出对细胞因子诱导的抑制作用，这些细胞因子由细胞内或细胞外的poly（I：C）诱导。然而，只有JNK抑制剂减少细胞内聚（I：C）诱导的黑素细胞死亡。综上所述，本研究提供了病毒因素在白癜风发病中的可能机制。
Viral factor has been implicated in the etiopathogenesis of vitiligo. To elucidate the effects of viral double-stranded RNA (dsRNA) on melanocytes and to explore the underlying mechanisms, primary cultured normal human melanocytes were treated with synthetic viral dsRNA analog poly(I:C). The results demonstrated that poly(I:C)-triggered apoptosis when transfected into melanocytes, while extracellular poly(I:C) did not have that effect. Intracellular poly(I:C)-induced melanocyte death was decreased by RIG-I or MDA5 siRNA, but not by TLR3 siRNA. Both intracellular and extracellular poly(I:C) induced the expression of IFNB, TNF, IL6, and IL8. However, extracellular poly(I:C) demonstrated a much weaker induction capacity of cytokine genes than intracellular poly(I:C). Further analysis revealed that phosphorylation of TBK1, IRF3, IRF7, and TAK1 was differentially induced by intra- or extracellular poly(I:C). NFκB inhibitor Bay 11-7082 decreased the induction of all the cytokines by poly(I:C), suggesting the ubiquitous role of NFκB in the process. Poly(I:C) treatment also induced the phosphorylation of p38 and JNK in melanocytes. Both JNK and p38 inhibitors showed suppression on the cytokine induction by intra- or extracellular poly(I:C). However, only the JNK inhibitor decreased the intracellular poly(I:C)-induced melanocyte death. Taken together, this study provides the possible mechanism of viral factor in the pathogenesis of vitiligo.