Abstract
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.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
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 / drug effects*
-
Microglia / metabolism
-
Nitric Oxide Synthase / metabolism
-
Nitric Oxide Synthase Type II
-
RNA, Messenger / metabolism
-
Receptors, Tumor Necrosis Factor / immunology
-
Receptors, Tumor Necrosis Factor, Type I
-
Recombinant Proteins / pharmacology
-
Reverse Transcriptase Polymerase Chain Reaction / methods
-
Tetrazolium Salts
-
Thiazoles
-
Tumor Necrosis Factor Decoy Receptors
-
Tumor Necrosis Factor-alpha / genetics
-
Tumor Necrosis Factor-alpha / metabolism
-
Tumor Necrosis Factor-alpha / pharmacology*
Substances
-
Antibodies
-
Cytokines
-
Lipopolysaccharides
-
RNA, Messenger
-
Receptors, Tumor Necrosis Factor
-
Receptors, Tumor Necrosis Factor, Type I
-
Recombinant Proteins
-
Tetrazolium Salts
-
Thiazoles
-
Tumor Necrosis Factor Decoy Receptors
-
Tumor Necrosis Factor-alpha
-
recombinant human tumor necrosis factor-binding protein-1
-
Nitric Oxide Synthase
-
Nitric Oxide Synthase Type II
-
Nos2 protein, mouse
-
Acid Phosphatase
-
thiazolyl blue