Complex Inflammation mRNA-Related Response in ALS Is Region Dependent.
Complex Inflammation mRNA-Related Response in ALS Is Region Dependent.
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DOI：
10.1155/2015/573784
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发表时间：
2015
影响因子：
3.1
通讯作者：
Ferrer I
中科院分区：
文献类型：
--
作者：
Berjaoui S;Povedano M;Garcia-Esparcia P;Carmona M;Aso E;Ferrer I
在典型的脊髓型ALS病例中，分析了脊髓前部和额叶皮质第8区的炎症变化。在脊髓前角和锥体束中发现星形胶质细胞和活化的小胶质细胞数量增加。与对照组相比，在ALS病例的前腰脊髓中发现TLR 7、CTSS和CTSC mRNA的表达显著增加，并且IL 10 RA、TGFB 1和TGFB 2的表达有增加的趋势，而C1 QTNF 7和TNFRSF 1A mRNA的表达水平显著降低。在ALS病例中，IL 6显著上调，而IL 1B在额叶皮层第8区的表达无显著增加。在ALS病例中，在散在的单核细胞衍生的巨噬细胞/小胶质细胞中发现IL-6免疫反应性，在少数来源不明的细胞中发现TNF-α。ALS患者脊髓腰段运动神经元中IL-1β表达增加，分布异常。强IL-10免疫反应共定位与TDP-43阳性包涵体在运动神经元ALS病例。目前的观察结果表明，ALS中炎症反应的细胞因子和介质的复杂参与与受影响神经元中促炎细胞因子的增加和抗炎IL-10的隔离一致。
Inflammatory changes are analyzed in the anterior spinal cord and frontal cortex area 8 in typical spinal-predominant ALS cases. Increased numbers of astrocytes and activated microglia are found in the anterior horn of the spinal cord and pyramidal tracts. Significant increased expression of TLR7, CTSS, and CTSC mRNA and a trend to increased expression of IL10RA, TGFB1, and TGFB2 are found in the anterior lumbar spinal cord in ALS cases compared to control cases, whereas C1QTNF7 and TNFRSF1A mRNA expression levels are significantly decreased. IL6 is significantly upregulated and IL1B shows a nonsignificant increased expression in frontal cortex area 8 in ALS cases. IL-6 immunoreactivity is found in scattered monocyte-derived macrophages/microglia and TNF-α in a few cells of unknown origin in ALS cases. Increased expression and abnormal distribution of IL-1β occurred in motor neurons of the lumbar spinal cord in ALS. Strong IL-10 immunoreactivity colocalizes with TDP-43-positive inclusions in motor neurons in ALS cases. The present observations show a complex participation of cytokines and mediators of the inflammatory response in ALS consistent with increased proinflammatory cytokines and sequestration of anti-inflammatory IL-10 in affected neurons.