Lipopolysaccharides-activated human astroglioma cells induce apoptotic death of T-lymphocytes via c-Jun N-terminal kinases-dependent up-regulation of TRAIL.
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.
Kwon
Daeho
D
Department of Pharmacology, College of Medicine, Division of Nano Science, Ewha Womans University, Seoul, Republic of Korea.
Cheong
Jae Hoon
JH
Lee
Jae-Chul
JC
Kwon
Jae-Hyun
JH
Kim
Won-Ki
WK
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D001253:Astrocytes / Q000276:immunology / Q000502:physiology*; D001254:Astrocytoma; D045744:Cell Line, Tumor; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases