We previously demonstrated that the inflammatory
cytokine interleukin-6 (IL-6) activates the
Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway in fibroblasts within the outer membranes of
chronic subdural hematomas (CSDHs), and the activation of this pathway may induce CSDH outer membrane growth. The inhibitory system for this signal transduction pathway is unknown. CSDH fluids were obtained from 10 patients during
trepanation surgery as the case group, and cerebrospinal fluid (CSF) samples were obtained from seven patients suffering from
subarachnoid hemorrhage (SAH) on Day 1 as the control group. The concentrations of
IL-6, soluble
IL-6 receptor (sIL-6R), and
soluble gp130 (
sgp130) in CSDH fluid and CSF were measured using
enzyme immunoassay kits. The co-localization of
IL-6 and
sgp130 in CSDH fluid was examined by immunoprecipitation. The expression levels of STAT3, JAK2, suppressor of
cytokine signaling 3 (SOCS3), and
protein inhibitor of activated Stat3 (PIAS3) in the outer membranes of CSDHs were examined by immunostaining. Soluble IL-6R and
sgp130 concentrations in CSDH fluid were significantly higher than those in CSF after SAH.
Sgp130 and
IL-6 were co-immunoprecipitated from CSDH fluid. Immunostaining revealed STAT3, JAK2, SOCS3, and PIAS3 expression in fibroblasts located in the outer membranes of CSDHs.
Soluble gp130 binds to IL-6/sIL-6R and acts as an antagonist of the JAK/STAT signaling pathway. SOCS3 also binds to JAK and inhibits its signaling pathway. In addition, PIAS3 regulates STAT3 activation. These factors might down-regulate the IL-6/JAK/STAT signaling pathway in fibroblasts within CSDH outer membranes. Therefore, these molecules may be novel therapeutic targets for the inhibition of CSDH growth.