Interleukin-6-induced S100B secretion is inhibited by haloperidol and risperidone

Abstract

Although inflammation may be a physiological defense process, imbalanced neuroinflammation has been associated with the pathophysiology of brain disorders, including major depression and schizophrenia. Activated glia releases a variety of pro-inflammatory cytokines that contribute to neuronal dysfunction. Elevated levels of S100B, a glia derived protein, have been observed in the serum and CSF of schizophrenic patients suggesting a glial role in the disease. We evaluated whether S100B secretion (in C6 glioma cells and hippocampal slices in Wistar rats) could be directly modulated by the main inflammatory cytokines (IL-1β, TNF-α, IL-6 and IL-8) altered in schizophrenia, as well as the possible involvement of mitogen-activated protein kinase (MAPK) pathways in these responses. We also investigated the effects of typical and atypical antipsychotic drugs on glial cytokine-induced S100B release. Our results suggest that S100B secretion is increased by pro-inflammatory cytokines via MAPK and that oxidative stress may be a component of this modulation. These results reinforce the idea that the S100B protein is involved in the inflammatory response observed in many brain diseases, including schizophrenia. Moreover the antipsychotics, haloperidol and risperidone, were able to inhibit the secretion of S100B following IL-6 stimulation in C6 glioma cells.

Venlafaxine ameliorates the depression-like behaviors and hippocampal S100B expression in a rat depression model

“…Recent studies reported that vatairea macrocarpa lectin (VML) caused an enhancement of S100B levels, trigger neuroinflammatory response in mouse hippocampus and exhibited a depressive-like activity [40], suggesting close relationships between the increased S100B and neuroinflammatory markers in the hippocampus and depressive-like behaviors. Some studies have indicated that higher blood levels of pro-inflammatory cytokines TNF-α and IL-6 in drug-free patients with depression [41, 42]. Moreover, the pro-inflammatory cytokines levels were normalized once antidepressant treatment was administered [43].…”

The S100B story: from biomarker to active factor in neural injury

“…The antipsychotics haloperidol and risperidone have been shown to be able to inhibit the secretion of S100B in C6 glioma cells following IL‐6 stimulation: this result has been interpreted as supporting the involvement of inflammatory processes in schizophrenia (de Souza et al . ). As an indirect indication that S100B may be involved in processes associated with structural brain changes in schizophrenia, a relationship between blood S100B levels and alterations in white matter (namely the posterior cingulate bundle and superior longitudinal fasciculus), as obtained from T1‐weighted MR‐images, has been reported in unmedicated schizophrenia patients (Milleit et al .…”

Natural product HTP screening for attenuation of cytokine-induced neutrophil chemo attractants (CINCs) and NO2− in LPS/IFNγ activated glioma cells

“…The study design in employs the use of a C6 glioma cell line to conduct the HTP screenings. C6 cells are of malignant origin and widely used to investigate neuro inflammation relevant to brain disorders, depression, AD, PD, schizophrenia (de Souza et al, 2013, Kawashima et al, 2008, Lykhmus et al, 2015) defects in iron metabolism (di Patti et al, 2004) glutamate uptake (dos Santos et al, 2006) multiple sclerosis (MS)(Harzheim et al, 2003) as well as therapies and processes associate with aggressive malignant tumor growth and invasion (Adach-Kilon et al, 2011, Li et al, 2016, Liau et al, 1998, Pineda et al, 2005). Glioma tumor growth is advanced by an inflammatory microenvironment involving inducible nitric oxide synthase (iNOS) leading to enhanced vasodilation, proliferation (Munoz-Fernandez and Fresno, 1993) migration (Yeh et al, 2012) and the rapid growth of GBMs (Cobbs et al, 2003).…”