LIGHT regulates CD86 expression on dendritic cells through NF-kappaB, but not JNK/AP-1 signal transduction pathway.
The members of the tumor necrosis factor (TNF) family play pivotal roles in the regulation of the immune system. LIGHT is a type II transmembrane protein belonging to the TNF family that was originally identified as a weak inducer of apoptosis. This cytokine has been extensively studied for its role in T cell regulation. Recently, we identified its role in inducing maturation of dendritic cells, such as LIGHT upregulated CD86 expression on dendritic cells in our previous report. However, the signal transduction pathway on this regulation remains unknown. In this study, we found that LIGHT activated NF-kappaB, p44/42 MAPK, but not JNK. LIGHT upregulates CD86 expression on DCs through activation of NF-kappaB, but not p44/42 signal pathway, because inhibition of NF-kappaB activity by its inhibitor could blunt the effect of LIGHT in up-regulation of CD86 expression, but neither inhibitor of p44/42 MAPK nor JNK inhibitor has this effect. Thus we demonstrate that LIGHT regulates CD86 expression through NF-kappaB signal transduction pathway but neither p44/42 MAPK nor JNK/AP-1 signaling pathway. We conclude that NF-kappaB signal plays a key role in LIGHT-mediated upregulation of CD86 expression.
Zou
Gang-Ming
GM
Section of Bone Marrow Transplantation, Rush University Medical Center, 2242 West Harrison St., Chicago, IL, USA. gzou@iupui.edu
Hu
Wen-Yang
WY
D051940:B7-2 Antigen / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D009000:Monocytes / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D051940:B7-2 Antigen; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D016328:NF-kappa B; C505914:TNFSF14 protein, human; D018808:Transcription Factor AP-1; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3