Role of TGF-beta in Survival of Phagocytizing Microglia: Autocrine Suppression of TNF-alpha Production and Oxidative Stress.
- Author:
Keun Young RYU
1
;
Geum Sil CHO
;
Hua Zi PIAO
;
Won Ki KIM
Author Information
- Publication Type:Original Article
- Keywords: microglia; LPS; phagocytosis; TNF-alpha; TGF-beta; ROS
- MeSH: Brain; Cytokines; Inflammation; Lipopolysaccharides; Microglia; Oxidative Stress; Phagocytosis; Polystyrenes; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha
- From:Experimental Neurobiology 2012;21(4):151-157
- CountryRepublic of Korea
- Language:English
- Abstract: 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-beta 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-alpha and TGF-beta 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-alpha and TGF-beta. However, while TNF-alpha production gradually decreased after 6 h, TGF-beta production remained at increased level. Microglial cells pre-treated with lipopolysaccharides (a strong immunostimulant, LPS) synergistically increased the production of TNF-alpha and TGF-beta both. However, LPS-pretreated microglia produced TNF-alpha in a more sustained manner and became more vulnerable, probably due to the marked and sustained production of TNF-alpha and reduced TGF-beta. Intracellular oxidative stress appears to change in parallel with the microglial production of TNF-alpha. These results indicate TGF-beta contributes for the survival of phagocytizing microglia through autocrine suppression of TNF-alpha production and oxidative stress.
