Expression and cellular distribution of the interleukin 2 signaling system in cortical lesions from patients with focal cortical dysplasia

摘要

Focal cortical dysplasia (FCD) is a well-known cause of medically intractable epilepsy. To understand the potential role of the inflammatory cytokine interleukin 2 (IL-2) in the pathogenesis of FCD, we investigated the expression patterns of IL-2 and its receptors (IL-2Rs) in FCD and control samples that included epileptic neocortex from mesial temporal lobe epilepsy patients and nonepileptic normal cortex (CTX). Greater mRNA and protein levels of IL-2 and IL-2Rs were observed in FCD versus CTX samples. Moreover, the expression of IL-2 and IL-2Rs was significantly higher in FCD II than FCD I. In situ hybridization and immunohistochemistry results indicated that IL-2 and IL-2Rs were strongly expressed in hypertrophic neurons and neuronal microcolumns in FCD I and highly expressed in malformed cells in FCD II. In addition, the protein levels of Janus kinase 1, Janus kinase 3, phosphorylated signal transducer and activator of transcription 5, which are important downstream factors in the IL-2 signaling pathway, were increased in FCD lesions. Soluble IL-2R was decreased in FCD compared with that in CTX samples. These results suggest that upregulation of IL-2 and IL-2Rs combined with activation of IL-2-dependent signaling pathways may contribute to the pathogenesis of FCD.