title: Expression of the interleukin 6 system in cortical lesions from patients with tuberous sclerosis complex and focal cortical dysplasia type IIb.
abstract: Tuberous sclerosis complex (TSC) and focal cortical dysplasia type IIb (FCDIIb) are characterized by epilepsy-associated cerebral cortical malformations. To understand the potential role of the inflammatory cytokine interleukin 6 (IL-6) in the pathogenesis of these lesions, we analyzed the IL-6 system in TSC and FCDIIb cortical lesions and in control cortex (CTX). Greater messenger RNA and protein levels of IL-6 and of its receptors (i.e. IL-6 receptor [IL-6R] and glycoprotein 130 [gp130]) were observed in TSC and FCDIIb lesions versus CTX. Immunohistochemical analyses indicated that IL-6 and IL-6R were strongly expressed in misshapen cells, namely, dysmorphic neurons, giant neurons, and balloon cells. Glycoprotein 130 was diffusely expressed in nearly all cell types. Most IL-6/IL-6R+ misshapen cells colabeled with neuronal rather than astrocytic markers, suggesting a neuronal lineage; most IL-6/IL-6R+ balloon cells in FCDIIb expressed glial fibrillary acidic protein. Protein levels of Janus kinase 2 and phosphorylated signal transducer and activator of transcription 3 were greater than in CTX, suggesting involvement of the gp130-Janus kinase 2-signal transducer and activator of transcription 3 pathway in IL-6 signal transduction. Soluble IL-6R, but not soluble gp130, was greater in TSC and FCDIIb lesions than in CTX, indicating activation of this trans-signaling pathway. These results suggest that overexpression in the IL-6 system and activation of IL-6 signal transduction pathways may contribute to the pathogenesis of cortical lesions in TSC and FCDIIb.
authors.affiliation: Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Shu
authors.forename: Chun-Qing
authors.initials: CQ
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Yin
authors.forename: Ning
authors.initials: N
authors.lastname: An
authors.forename: Shi-Yong
authors.initials: SY
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
mesh_terms: D002452:Cell Count / Q000379:methods; D002540:Cerebral Cortex / Q000293:injuries* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D050822:Cytokine Receptor gp130 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007223:Infant; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D054220:Malformations of Cortical Development / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D014402:Tuberous Sclerosis / Q000473:pathology*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130