Lipopolysaccharides-activated human astroglioma cells induce apoptotic death of T-lymphocytes via c-Jun N-terminal kinases-dependent up-regulation of TRAIL

Abstract

In the present study, we report that activated human astroglioma cells can injure T-lymphocytes by producing tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). Treatment with lipopolysaccharides (LPS), a well-known immune stimulator, increased the expression levels of TRAIL mRNA and protein in human astroglioma cells. The increase of TRAIL mRNA expression by LPS was preceded by phosphorylation of the c-Jun N-terminal kinase (JNK) and consequently abrogated in the presence of the specific JNK inhibitor SP600125. The up-regulation of TRAIL expression was well co-related with AP-1 activation. Activated human astroglioma cells markedly induced the apoptotic death of T-lymphocytes. Pre-treatment with the TRAIL antagonistic protein TRAIL-R2:Fc prevented the death of T-lymphocytes caused by activated human astroglioma cells. The present results suggest that astroglioma cells may down-regulate T-lymphocytes via up-regulation of TRAIL. © 2006 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.