Autocrine activation of microglia by tumor necrosis factor-alpha

J Neuroimmunol. 2005 May;162(1-2):89-96. doi: 10.1016/j.jneuroim.2005.01.015.

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