Department of Neurology, The University of Iowa, Iowa City, IA, USA.
Neurochem Int. 2012 Feb;60(3):215-9. doi: 10.1016/j.neuint.2011.12.011. Epub 2011 Dec 30.
The role of glia maturation factor (GMF) in myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide-induced experimental autoimmune encephalomyelitis (EAE) was investigated using GMF-deficient (GMF-KO) mice. We demonstrate that GMF-KO mice were resistant to the MOG 35-55 peptide-induced EAE as compared to wild type (Wt) mice (two in eight versus 10 in 10). Next, we examined the effect of administration of recombinant human GMF (rGMF) on MOG 35-55 peptide-induced EAE in mice. Daily administration of rGMF, staring days 1-14, resulted in significant exacerbation of clinical symptoms. Following rGMF injections, both GMF-KO (six in eight) and Wt mice (eight in eight) developed severe EAE (maximal clinical score of 3.5-4.0) with high frequency. The histological examination revealed severe infiltration of inflammatory cells in the spinal cord of MOG-immunized Wt mice while the resistance to EAE in GMF-KO mice was characterized by the absence of inflammatory cells. Administration of rGMF in Wt mice and GMF-KO mice resulted in a significant increase in infiltrating cells in the spinal cord following MOG-immunizations. We also evaluated cytokines and chemokines production as parameters of severity of inflammation in the spinal cord of Wt versus GMF-KO mice with and without GMF-reconstitution following MOG-immunizations. Cytokines (TNF-α, IFN-γ, IL-1β, IL-6) and chemokines (CCL2, CCL3, CXCL10, GM-CSF) production were significantly greater in Wt mice than in GMF-KO mice following MOG-immunization. Furthermore, the reconstitution experiment with rGMF showed that the administration of rGMF in both, Wt mice and GMF-KO mice produced significant increase in the GMF-mediated cytokine/chemokine production.
研究了神经胶质细胞成熟因子（GMF）在髓鞘少突胶质细胞糖蛋白（MOG）35-55 肽诱导的实验性自身免疫性脑脊髓炎（EAE）中的作用，方法是使用 GMF 缺陷（GMF-KO）小鼠。与野生型（WT）小鼠（10 只中有 2 只）相比，我们发现 GMF-KO 小鼠对 MOG 35-55 肽诱导的 EAE 具有抗性（8 只中有 2 只）。接下来，我们研究了重组人 GMF（rGMF）对 MOG 35-55 肽诱导的 EAE 小鼠的影响。rGMF 每天给药（第 1-14 天）可显著加重临床症状。rGMF 注射后，GMF-KO（8 只中有 6 只）和 WT 小鼠（8 只中有 8 只）均发展为严重的 EAE（临床评分最高为 3.5-4.0），频率较高。组织学检查显示，MOG 免疫的 WT 小鼠脊髓中有严重的炎症细胞浸润，而 GMF-KO 小鼠对 EAE 的抗性则以无炎症细胞为特征。rGMF 在 WT 小鼠和 GMF-KO 小鼠中的给药导致 MOG 免疫后脊髓中浸润细胞的显著增加。我们还评估了 WT 小鼠和 GMF-KO 小鼠在 MOG 免疫后 GMF 再构成前后，作为炎症严重程度参数的脊髓中细胞因子和趋化因子的产生。与 GMF-KO 小鼠相比，MOG 免疫后，WT 小鼠的细胞因子（TNF-α、IFN-γ、IL-1β、IL-6）和趋化因子（CCL2、CCL3、CXCL10、GM-CSF）的产生显著增加。此外，rGMF 的再构成实验表明，rGMF 在 WT 小鼠和 GMF-KO 小鼠中的给药均导致 GMF 介导的细胞因子/趋化因子产生显著增加。
