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Mol. Cells 2010; 30(1): 51-57

Published online July 31, 2010

https://doi.org/10.1007/s10059-010-0087-y

© The Korean Society for Molecular and Cellular Biology

Suppression of Lipopolysaccharide-Induced Microglial Activation by a Benzothiazole Derivative

Eun-A Kim1,2,6, Hanwook Kim1,6, Jee-Yin Ahn3, Hoh-Gyu Hahn4, Key-Sun Kim5, Tae Ue Kim2,
and Sung-Woo Cho1,*

1Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Korea, 2Department of Biomedical Laboratory Science, Yonsei University, Wonju 222-701, Korea, 3Department of Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea, 4Division of Life Sciences, Korea Institute of Science and Technology, Seoul 136-791, Korea, 5Center for Neural Science, Korea Institute of Science and Technology, Seoul 136-791, Korea, 6These authors contributed equally to this work.

Correspondence to : *Correspondence: swcho@amc.seoul.kr

Received: January 13, 2010; Revised: March 11, 2010; Accepted: March 25, 2010

Abstract

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.

Keywords cytokines, Glia, KHG21834, MAP kinases, neuroinflammation

Article

Research Article

Mol. Cells 2010; 30(1): 51-57

Published online July 31, 2010 https://doi.org/10.1007/s10059-010-0087-y

Copyright © The Korean Society for Molecular and Cellular Biology.

Suppression of Lipopolysaccharide-Induced Microglial Activation by a Benzothiazole Derivative

Eun-A Kim1,2,6, Hanwook Kim1,6, Jee-Yin Ahn3, Hoh-Gyu Hahn4, Key-Sun Kim5, Tae Ue Kim2,
and Sung-Woo Cho1,*

1Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Korea, 2Department of Biomedical Laboratory Science, Yonsei University, Wonju 222-701, Korea, 3Department of Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea, 4Division of Life Sciences, Korea Institute of Science and Technology, Seoul 136-791, Korea, 5Center for Neural Science, Korea Institute of Science and Technology, Seoul 136-791, Korea, 6These authors contributed equally to this work.

Correspondence to:*Correspondence: swcho@amc.seoul.kr

Received: January 13, 2010; Revised: March 11, 2010; Accepted: March 25, 2010

Abstract

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.

Keywords: cytokines, Glia, KHG21834, MAP kinases, neuroinflammation

Mol. Cells
Nov 30, 2022 Vol.45 No.11, pp. 763~867
COVER PICTURE
Naive (cyan) and axotomized (magenta) retinal ganglion cell axons in Xenopus tropicalis (Choi et al., pp. 846-854).

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