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Activation of JAK-STAT3 signaling pathway in chronic subdural hematoma outer membranes
Koji Osuka1, Yasuo Watanabe, Nobuteru Usuda
1Department of Neurological Surgery, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
Insights
Interleukin-6 (IL-6) activates the JAK1-STAT3 pathway in chronic subdural hematoma (CSDH) outer membranes. This dominant signaling pathway in fibroblasts may drive CSDH progression.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Chronic subdural hematoma (CSDH) is an inflammatory condition with incompletely understood mechanisms.
- Interleukin-6 (IL-6), a key inflammatory cytokine, is present in CSDH fluid and regulates the JAK-STAT signaling pathway.
Purpose of the Study:
- To investigate the role of the janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway in human CSDH outer membranes.
- To determine if IL-6 influences this pathway in CSDH.
Main Methods:
- Outer membranes from CSDH patients were analyzed using Western blot and immunohistochemistry.
- IL-6 concentrations in CSDH fluid were measured via enzyme immunoassay.
- Expression and phosphorylation of STAT1 and STAT3 were assessed.
Main Results:
- IL-6 levels were significantly elevated in CSDH fluid compared to control cerebrospinal fluid.
- JAK1, STAT1, and STAT3 were detected in all CSDH outer membrane samples.
- Phosphorylated STAT3 (p-STAT3) at Tyr(705) was significantly higher than phosphorylated STAT1 (p-STAT1) at Tyr(701).
- p-STAT3 was found in fibroblast nuclei within CSDH membranes.
Conclusions:
- The JAK1-STAT3 signaling pathway is predominantly activated in fibroblasts of human CSDH outer membranes.
- IL-6 may activate this pathway, suggesting its critical role in the progression of CSDH.
Abstract:
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.
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