Original Article

Exp Neurobiol 2012; 21(4): 151-157

Published online December 30, 2012

© The Korean Society for Brain and Neural Sciences

Role of TGF-β in Survival of Phagocytizing Microglia: Autocrine Suppression of TNF-α Production and Oxidative Stress

Keun-Young Ryu1, Geum-Sil Cho2, Hua Zi Piao3 and Won-Ki Kim2*

1College of Medicine, Korea University, Seoul 136-705, 2Department of Neuroscience, College of Medicine, Korea University, Seoul 136-705, Korea, 3Department of Pharmacology, College of Medicine, Yanbian University, Yanji 133002, China

Correspondence to: *To whom correspondence should be addressed.
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Microglia are recognized as residential macrophageal cells in the brain. Activated microglia play a critical role in removal of dead or damaged cells through phagocytosis activity. During phagocytosis, however, microglia should survive under the harmful condition of self-producing ROS and pro-inflammatory mediators. TGF-β has been known as a classic anti-inflammatory cytokine and controls both initiation and resolution of inflammation by counter-acting inflammatory cytokines. In the present study, to understand the self-protective mechanism, we studied time-dependent change of TNF-α and TGF-β production in microglia phagocytizing opsonized-beads (i.e., polystyrene microspheres). We found that microglia phagocytized opsonized-bead in a time-dependent manner and simultaneously produced both TNF-α and TGF-β. However, while TNF-α production gradually decreased after 6 h, TGF-β production remained at increased level. Microglial cells pre-treated with lipopolysaccharides (a strong immunostimulant, LPS) synergistically increased the production of TNF-α and TGF-β both. However, LPS-pretreated microglia produced TNF-α in a more sustained manner and became more vulnerable, probably due to the marked and sustained production of TNF-α and reduced TGF-β. Intracellular oxidative stress appears to change in parallel with the microglial production of TNF-α. These results indicate TGF-β contributes for the survival of phagocytizing microglia through autocrine suppression of TNF-α production and oxidative stress.

Keywords: microglia, LPS, phagocytosis, TNF-α, TGF-β, ROS