Autocrine activation of microglia by tumor necrosis factor-alpha.
In the central nervous system (CNS), tumor necrosis factor-alpha (TNF-alpha) derived from activated microglia plays a critical role as an inflammatory mediator. In this study, we examined the function of TNF-alpha as an autocrine mediator in microglial activation. TNF-alpha induced TNF-alpha production by microglia through ligation of TNF receptor 1 (TNFR1). TNF-alpha also increased the production of other inflammatory mediators. The activation of microglia by lipopolysaccharide is partially mediated by microglia-derived TNF-alpha. These findings suggest the existence of a positive feedback loop in the activation of microglia via TNF-alpha. This autocrine loop may be involved in the prolonged activation of microglia.
Kuno
Reiko
R
Department of Neuroimmunology, Institute of Environmental Medicine, Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan.
Wang
Jinyan
J
Kawanokuchi
Jun
J
Takeuchi
Hideyuki
H
Mizuno
Tetsuya
T
Suzumura
Akio
A
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D019898:Autocrine Communication / Q000187:drug effects*; D015152:Blotting, Northern / Q000379:methods; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013778:Tetrazolium Salts; D013844:Thiazoles; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D000906:Antibodies; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; C069521:recombinant human tumor necrosis factor-binding protein-1; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D000135:Acid Phosphatase; C022616:thiazolyl blue