Department of Neurological Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
Neurosci Lett. 2013 Feb 8;534:166-70. doi: 10.1016/j.neulet.2012.11.011. Epub 2012 Nov 19.
Chronic subdural hematoma (CSDH) is an inflammatory disease, the mechanism of which still remains to be elucidated. Interleukin-6 (IL-6), one of the inflammatory cytokines regulating janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, is expressed in human CSDH fluid. The status of this signaling pathway in human CSDH outer membranes was examined in the present study using outer membranes obtained during trepanation surgery. Concentrations of IL-6 in human CSDH fluids were measured using an enzyme immuno-assay kit. Expression patterns of JAK1, STAT1, phosphorylated (p)-STAT1 at Tyr(701) and at Ser(727), STAT3, p-STAT3 at Tyr(705) and at Ser(727) and actin in outer membranes were examined by Western blot analysis and immunohistochemistry. IL-6 is significantly expressed in human CSDH fluids compared with control cerebrospinal fluid. JAK1, STAT1 and STAT3 were detected in all cases. The expression of p-STAT3 at Tyr(705) is more significant compared with that of p-STAT1 at Tyr(701). In some cases, p-STAT3 at Ser(727) could also be detected, while p-STAT1 at Ser(727) could not. The localizations of STAT1 and STAT3 were revealed to be present in fibroblasts in human CSDH outer membranes, especially when p-STAT3 at Tyr(705) was in the nuclei of fibroblasts. These findings suggest that JAK1-STAT3 signaling is dominantly activated in fibroblasts of human CSDH outer membranes compared with STAT1 and indicate the possibility that this JAK1-STAT3 pathway might be activated by IL-6 and play a critical role in progression of human CSDH.
慢性硬脑膜下血肿（CSDH）是一种炎症性疾病，其发病机制尚不清楚。白细胞介素 6（IL-6）是调节 Janus 激酶（JAK）-信号转导子和转录激活子（STAT）信号通路的炎症细胞因子之一，在人 CSDH 液中表达。本研究采用钻孔术中获得的外膜，检测人 CSDH 外膜中该信号通路的状态。采用酶联免疫吸附试验试剂盒测定人 CSDH 液中 IL-6 的浓度。通过 Western blot 分析和免疫组织化学法检测外膜中 JAK1、STAT1、磷酸化（p）-STAT1（Tyr701 和 Ser727）、STAT3、p-STAT3（Tyr705 和 Ser727）和肌动蛋白的表达模式。与对照脑脊液相比，IL-6 在人 CSDH 液中明显表达。所有病例均检测到 JAK1、STAT1 和 STAT3。与 Tyr701 处的 p-STAT1 相比，p-STAT3（Tyr705）的表达更为显著。在某些情况下，还可以检测到 p-STAT3（Ser727），而 p-STAT1（Ser727）则不能。STAT1 和 STAT3 的定位显示存在于人 CSDH 外膜中的成纤维细胞中，尤其是当 Tyr705 处的 p-STAT3 存在于成纤维细胞的核内时。这些发现表明，与 STAT1 相比，JAK1-STAT3 信号在人 CSDH 外膜中的成纤维细胞中被明显激活，并表明该 JAK1-STAT3 途径可能被 IL-6 激活，并在人 CSDH 的进展中发挥关键作用。
