Interleukin-27 expression following infection with the murine gammaherpesvirus 68.
Interleukin-27 expression following infection with the murine gammaherpesvirus 68.
复制标题
DOI：
10.1016/j.cyto.2010.04.015
复制
发表时间：
2010-08
期刊：
影响因子：
3.8
通讯作者：
D. A. Nelson;Melanie D. Tolbert;M. Clemens;K. Bost
中科院分区：
文献类型：
--
作者：
D. A. Nelson;Melanie D. Tolbert;M. Clemens;K. Bost
IL-27是由p28和Epstein巴尔病毒诱导基因3（Ebi 3）蛋白亚基组成的异二聚体细胞因子。在本研究中，我们质疑鼠γ疱疹病毒68（HV-68）是否可以诱导Ebi 3，p28和IL-27在这种小鼠模型的EBV样感染的表达。培养的巨噬细胞和树突状细胞暴露于HV-68上调p28 mRNA的表达，并增加分泌的p28和IL-27（p28+ Ebi 3）蛋白。B220+和CD 11b+细胞在体内感染该病毒后也上调p28 mRNA表达。令人惊讶的是，在疾病的急性或单核细胞增多症阶段，在体内没有观察到p28或IL-27蛋白产生的显著增加。HV-68诱导的p28 mRNA表达上调引发细胞分泌IL-27的可能性由TLR 4激动剂增加细胞因子产生的能力提出。当培养的巨噬细胞和树突状细胞暴露于病毒加次优剂量的LPS时，观察到p28蛋白表达水平增加。更重要的是，当潜伏感染的小鼠用亚致死剂量的LPS攻击时，发生了p28和IL-27蛋白的产生增加。使用脓毒症模型，与单独感染或盲肠结扎和穿孔的小鼠相比，潜伏感染HV-68的小鼠具有夸大的p28蛋白产生。总之，这些研究确定了HV-68诱导的IL-27的表达，并表明当面对能够诱导IL-12家族细胞因子的该成员的其他刺激时，潜伏感染该γ疱疹病毒的小鼠将具有夸大的反应。
IL-27 is a heterodimeric cytokine composed of p28 and Epstein Barr virus induced gene 3 (Ebi3) protein subunits. In the present study, we questioned whether murine gammaherpesvirus 68 (HV-68) could induce expression of Ebi3, p28, and IL-27 in this mouse model of an EBV-like infection. Cultured macrophages and dendritic cells exposed to HV-68 upregulated p28 mRNA expression and increased secretion of the p28 and IL-27 (p28+Ebi3) proteins. B220+and CD11b+cells also upregulated p28 mRNA expression following in vivo infection with this virus. Surprisingly, no significant increases in p28 or IL-27 protein production were observed in vivo during the acute or mononucleosis phases of the disease. The possibility that HV-68-induced upregulation of p28 mRNA expression primed cells for IL-27 secretion was suggested by the ability of a TLR4 agonist to augment cytokine production. When cultured macrophages and dendritic cells were exposed to virus plus a suboptimal dose of LPS, increased levels of p28 protein expression were observed. More importantly, when latently infected mice were challenged with a sublethal dose of LPS, augmented p28 and IL-27 protein production occurred. Using a model of sepsis, mice latently infected with HV-68 had exaggerated p28 protein production when compared to mice that were singularly infected or subjected to cecal ligation and puncture. Taken together, these studies define expression of HV-68 induced IL-27, and suggest that mice latently infected with this gammaherpesvirus will have exaggerated responses when confronted with other stimuli capable of inducing this member of the IL-12 family of cytokines.