Autocrine activation of microglia by tumor necrosis factor-α

In the central nervous system (CNS), tumor necrosis factor-α (TNF-α) derived from activated microglia plays a critical role as an inflammatory mediator. In this study, we examined the function of TNF-α as an autocrine mediator in microglial activation. TNF-α induced TNF-α production by microglia thr...

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Bibliographic Details
Published in:Journal of neuroimmunology 2005-05, Vol.162 (1), p.89-96
Main Authors: Kuno, Reiko, Wang, Jinyan, Kawanokuchi, Jun, Takeuchi, Hideyuki, Mizuno, Tetsuya, Suzumura, Akio
Format: Article
Language:English
Subjects:
Acid Phosphatase - metabolism
Animals
Animals, Newborn
Antibodies - pharmacology
Autocrine Communication - drug effects
Blotting, Northern - methods
Cells, Cultured
Cytokines - metabolism
Dose-Response Relationship, Drug
Drug Interactions
Enzyme-Linked Immunosorbent Assay - methods
Gene Expression Regulation - drug effects
Lipopolysaccharides - pharmacology
Mice
Mice, Inbred C57BL
Microglia
Microglia - drug effects
Microglia - metabolism
Nitric Oxide Synthase - metabolism
Nitric Oxide Synthase Type II
Receptors, Tumor Necrosis Factor - immunology
Receptors, Tumor Necrosis Factor, Type I
Recombinant Proteins - pharmacology
Reverse Transcriptase Polymerase Chain Reaction - methods
RNA, Messenger - metabolism
Tetrazolium Salts
Thiazoles
TNFR1(p55)
TNFR2(p75)
Tumor Necrosis Factor Decoy Receptors
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - metabolism
Tumor Necrosis Factor-alpha - pharmacology
Tumor necrosis factor-α (TNF-α)
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Summary:In the central nervous system (CNS), tumor necrosis factor-α (TNF-α) derived from activated microglia plays a critical role as an inflammatory mediator. In this study, we examined the function of TNF-α as an autocrine mediator in microglial activation. TNF-α induced TNF-α production by microglia through ligation of TNF receptor 1 (TNFR1). TNF-α also increased the production of other inflammatory mediators. The activation of microglia by lipopolysaccharide is partially mediated by microglia-derived TNF-α. These findings suggest the existence of a positive feedback loop in the activation of microglia via TNF-α. This autocrine loop may be involved in the prolonged activation of microglia.
ISSN:0165-5728
1872-8421
DOI:10.1016/j.jneuroim.2005.01.015