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KMID : 0578320100300010051
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Molecules and Cells
2010 Volume.30 No. 1 p.51 ~ p.57
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Suppression of Lipopolysaccharide-Induced Microglial Activation by a Benzothiazole Derivative
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Kim Eun-A
Kim Han-Wook
Ahn Jee-Yin
Hahn Hoh-Gyu
Kim Key-Sun
Kim Tae-Ue
Cho Sung-Woo
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Abstract
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We previously reported that KHG21834, a benzothiazole derivative, attenuates the beta-amyloid (Aβ)-induced degeneration of both cortical and mesencephalic neurons in vitro. Central nervous system inflammation mediated by activated microglia is a key event in the development of neurodegenerative disease. In this study, we show that KHG21834 suppresses inflammation-mediated cytokine upregulation. Specifically, KHG21834 induces significant reductions in the lipopolysaccharide-induced activation of microglia and production of proinflammatory mediators such as tumor necrosis factor-α , interlukin-1β, nitric oxide, and inducible nitric oxide synthase. In addition, KHG21834 blocks the expression of mitogen-activated protein kina-ses, including ERK, p38 MAPK, JNK, and Akt. In vivo intra-cerebroventricular infusion of KHG21834 also leads to decreases the level of interleukin-1β and tumor necrosis factor-α in brain. These results, in combination with our previous findings on Aβ-induced degeneration, support the potential therapeutic efficacy of KHG21834 for the treatment of neurodegenerative disorders via the targeting of key glial activation pathways.
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KEYWORD
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cytokines, Glia, KHG21834, MAP kinases, neuroinflammation
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