Activated microglial supernatant induced motor neuron cytotoxicity is associated with upregulation of the TNFR1 receptor.
We have previously reported that supernatant derived from LPS-activated BV-2 cells, an immortalized microglial cell line, induces death of NSC-34 cells (a motor neuron hybridoma) through a TNFalpha and nitric oxide synthase (NOS) dependant mechanism. In this study, we have observed that LPS-activated BV-2 supernatant induces NSC-34 cell death in association with an upregulation of the TNF receptor 1 (TNFR1) expression on NSC-34 cells, both at the transcription level and at the cell surface protein level. The upregulation of TNFR1 receptor was independent of TNFalpha, and could be partly inhibited by the inhibition of iNOS activation in the BV-2 cells. The TNFR2 receptor was not involved. These observations have important implications in understanding the mechanism by which microglial activation contributes to the motor neuron degeneration.
Wen
Weiyan
W
Cell Biology Research Group, Robarts Research Institute, London, Ont., Canada.
Sanelli
Teresa
T
Ge
Weiwen
W
Strong
Wendy
W
Strong
Michael J
MJ
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique / Q000379:methods; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009046:Motor Neurons / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects*
D000906:Antibodies; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C022616:thiazolyl blue