Activation of Autophagy Pathway Suppresses the Expression of iNOS, IL6 and Cell Death of LPS-Stimulated Microglia Cells
Han Hye-Eun, 김태경, 손형진, 박우진, 한평림,
소속 상세정보
( Han Hye-Eun )
Gwangju Institute of Science and Technology Department of Life Science
김태경 ( Kim Tae-Kyung )
Ewha Womans University Department of Brain and Cognitive Sciences
손형진 ( Son Hyung-Jin )
Ewha Womans University Department of Brain and Cognitive Sciences
박우진 ( Park Woo-Jin )
Gwangju Institute of Science and Technology Department of Life Science
한평림 ( Han Pyung-Lim )
Ewha Womans University Department of Brain and Cognitive Sciences
KMID : 0606920130210010021
Abstract
Microglia play a role in maintaining and resolving brain tissue homeostasis. In pathological conditions, microglia release pro-inflammatory cytokines and cytotoxic factors, which aggravate the progression of neurodegenerative diseases. Autophagy pathway might be involved in the production of pro-inflammatory cytokines and cytotoxic factors in microglia, though details of the mechanism remain largely unknown. In the present study, we examined the role of the autophagy pathway in activated BV2 microglia cells. In BV2 cells, rapamycin treatment activated the formation of anti-LC3-labeled autophagosomes, whereas the ATG5 depletion using siRNA-ATG5 prevented the formation of LC3-labeled autophagosomes, indicating that BV2 cells exhibit an active classical autophagy system. When treated with LPS, BV2 cells expressed an increase of anti-LC3-labeled dots. The levels of LC3-labeled dots were not suppressed, instead tended to be enhanced, by the inhibition of the autophagy pathway with siRNA-ATG5 or wortmannin, suggesting that LPS-induced LC3-labeled dots in nature were distinct from the typical autophagosomes. The levels of LPS-induced expression of iNOS and IL6 were suppressed by treatment with rapamycin, and conversely, their expressions were enhanced by siRNA-ATG5 treatment. Moreover, the activation of the autophagy pathway using rapamycin inhibited cell death of LPS-stimulated microglia. These results suggest that although microglia possess a typical autophagy pathway, the glial cells express a non-typical autophagy pathway in response to LPS, and the activation of the autophagy pathway suppresses the expression of iNOS and IL6, and the cell death of LPS-stimulated microglia.
키워드
Autophagy; LPS; iNOS; IL6; Microglia
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