Cellular iron status influences the functional relationship between microglia and oligodendrocytes

X. Zhang, N. Surguladze, B. Slagle-Webb, A. Cozzi, James R. Connor

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Previously, we have reported that there is a spatiotemporal relationship between iron accumulation in microglia and oligodendrocytes during normal development and in remyelination following injury. This in vivo observation has prompted us to develop a cell culture model to test the relationship between iron status of microglia and survival of oligodendrocytes. We found that conditioned media from iron-loaded microglia increases the survival of oligodendrocytes; but conditioned media from iron loaded activated microglia is toxic to oligodendrocytes. In the trophic condition, one of the proteins released by iron-loaded microglia is H-ferritin, and transfecting the microglia with siRNA for H-ferritin blocks the trophic response on oligodendrocytes. Lipopolysaccharide (LPS) activation decreases the amount of H-ferritin that is released from microglia and increases the release of the proinflammatory cytokines tumor necrosis factor-α and interleukin-1. LPS activation of iron-enriched microglia results in the activation of NF-kB and greater release of cytokines when compared with that of control microglia; whereas treating microglia with an iron chelator is associated with less NF-kB activation and less release of cytokines. These results indicate that microglia play an important role in iron homoeostasis and that their iron status can influence how microglia influence growth and survival of oligodendrocytes. The results further indicate that ferritin, released by microglia, is a significant source of iron for oligodendrocytes.

Original languageEnglish
Pages (from-to)795-804
Number of pages10
JournalGLIA
Volume54
Issue number8
DOIs
Publication statusPublished - Dec 2006

Fingerprint

Oligodendroglia
Microglia
Iron
Apoferritins
NF-kappa B
Conditioned Culture Medium
Cytokines
Lipopolysaccharides
Poisons
Ferritins
Chelating Agents
Interleukin-1
Small Interfering RNA
Homeostasis
Cell Culture Techniques
Tumor Necrosis Factor-alpha
Observation

Keywords

  • Glia
  • Inflammation
  • Metals
  • Myelin disorders
  • Neurodegenerative diseases
  • Trophic factors

ASJC Scopus subject areas

  • Immunology

Cite this

Cellular iron status influences the functional relationship between microglia and oligodendrocytes. / Zhang, X.; Surguladze, N.; Slagle-Webb, B.; Cozzi, A.; Connor, James R.

In: GLIA, Vol. 54, No. 8, 12.2006, p. 795-804.

Research output: Contribution to journalArticle

Zhang, X. ; Surguladze, N. ; Slagle-Webb, B. ; Cozzi, A. ; Connor, James R. / Cellular iron status influences the functional relationship between microglia and oligodendrocytes. In: GLIA. 2006 ; Vol. 54, No. 8. pp. 795-804.
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