Activation of Signal Transducer and Activator of Transcription 3 in Endothelial Cells of Chronic Subdural Hematoma Outer Membranes.
OBJECTIVE
Chronic subdural hematoma (CSDH) is considered an angiogenic and inflammatory disease. Interleukin-6, a well-known inflammatory cytokine, activates the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. We previously reported that the JAK/STAT pathway is activated in fibroblasts in the outer membrane of CSDH. More recently, signal transducer and activator of transcription 3 (STAT3) has been shown to have a role in angiogenesis. We examined the expression of STAT3 in endothelial cells in the outer membrane of CSDH.


METHODS
This study included 7 patients whose outer membranes were successfully obtained during trephination surgery. The expression of STAT3 and phosphorylated STAT3 was examined by Western blot analysis and immunohistochemistry. We also examined whether CSDH fluid could activate STAT3 in cultured endothelial cells in vitro.


RESULTS
STAT3 and phosphorylated STAT3 were detected in all cases. Immunostaining showed that STAT3 and phosphorylated STAT3 were expressed not only in fibroblasts but also in vascular endothelium. Expression of phosphorylated STAT3 in endothelial cells was significantly induced immediately after treatment of CSDH fluid in vitro. The activation of STAT3 was significantly inhibited by treatment with antibodies that were directed against interleukin-6; however, this was suppressed by antibodies that were directed against vascular endothelial growth factor, but not significantly.


CONCLUSIONS
Interleukin-6 might dominantly activate STAT3 in endothelial cells, which might have a central role in endothelial cell proliferation and angiogenesis of CSDH outer membranes.
Department of Neurological Surgery, Aichi Medical University, Aichi, Japan. Electronic address: kosuka@aichi-med-u.ac.jp.
Koji
K
Osuka
High Technology Research Center, Pharmacology, Showa Pharmaceutical University, Tokyo, Japan.
Yasuo
Y
Watanabe
Department of Anatomy II, Fujita Health University School of Medicine, Aichi, Japan.
Nobuteru
N
Usuda
Department of Neurological Surgery, Aichi Medical University, Aichi, Japan.
Masahiro
M
Aoyama
Department of Neurological Surgery, Aichi Medical University, Aichi, Japan.
Reo
R
Kawaguchi
Department of Neurological Surgery, Aichi Medical University, Aichi, Japan.
Takeya
T
Watabe
Department of Neurological Surgery, Aichi Medical University, Aichi, Japan.
Masakazu
M
Takayasu
D000368:Aged; D015153:Blotting, Western; D002478:Cells, Cultured; D002908:Chronic Disease; D006259:Craniocerebral Trauma / Q000150:complications; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D020200:Hematoma, Subdural, Chronic / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D008297:Male; D008875:Middle Aged; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A
Angiogenesis; Chronic subdural hematoma; STAT3