Hooper Laura C, Chin Marian S, Detrick Barbara, Hooks John J
Laboratory of Immunology, Immunology and Virology Section, National Eye Institute, National Institutes of Health, NIH Bldg 10, Rm 6N228, 10 Center Drive, Bethesda, MD 20892, USA.
J Neuroimmunol. 2005 Sep;166(1-2):65-74. doi: 10.1016/j.jneuroim.2005.05.018.
Experimental coronavirus retinopathy (ECOR) is a virally triggered model of retinal degeneration composed of both genetic and autoimmune components. Since TNF-alpha plays a role in immune-mediated processes we evaluated the levels of TNF-alpha/TNF-alpha receptors and the downstream signaling molecule nitric oxide (NO) during disease in both retinal degeneration susceptible BALB/c and degeneration resistant CD-1 mice. Following coronavirus injection, TNF-alpha mRNA was detected at higher levels within the retinas, and concentrations of TNF-alpha (p<0.005) and sTNFR1 (p<0.0005) proteins were increased within the sera of BALB/c but not CD-1 mice. While concentrations of sTNFR2 proteins were elevated in both BALB/c (p<0.00005) and CD-1 (p<0.005) mice compared to controls, concentrations were higher in BALB/c mice (p<0.0005). Gene expression of iNOS while initially high in BALB/c mice decreased during the acute phase of infection, while it increased in CD-1 mice. These trends are attributable to differences in monocyte TNFR2 release (p<0.0005) between the strains since sTNFR2 decreased (p<0.01) levels of NO production. These studies demonstrate that retinal degeneration following viral infection is associated with increased release of TNF-alpha/TNF receptors combined with a down-regulation of NO. Furthermore they suggest that these molecules are involved in alterations in immune response leading to autoimmune reactivity.
实验性冠状病毒视网膜病变（ECOR）是一种由遗传和自身免疫成分组成的病毒引发的视网膜变性模型。由于肿瘤坏死因子-α（TNF-α）在免疫介导过程中发挥作用，我们评估了视网膜变性易感的BALB/c小鼠和抗变性的CD-1小鼠在疾病过程中TNF-α/TNF-α受体水平以及下游信号分子一氧化氮（NO）的情况。注射冠状病毒后，在视网膜内检测到TNF-α mRNA水平较高，并且在BALB/c小鼠血清中TNF-α（p<0.005）和可溶性TNF受体1（sTNFR1，p<0.0005）蛋白浓度升高，但CD-1小鼠血清中未升高。与对照组相比，BALB/c小鼠（p<0.00005）和CD-1小鼠（p<0.005）血清中sTNFR2蛋白浓度均升高，且BALB/c小鼠浓度更高（p<0.0005）。诱导型一氧化氮合酶（iNOS）基因表达在BALB/c小鼠感染急性期开始时较高，但随后下降，而在CD-1小鼠中则升高。这些趋势归因于不同品系之间单核细胞TNFR2释放的差异（p<0.0005），因为sTNFR2降低了NO产生水平（p<0.01）。这些研究表明，病毒感染后的视网膜变性与TNF-α/TNF受体释放增加以及NO下调有关。此外，它们表明这些分子参与了导致自身免疫反应性的免疫反应改变。
