A dibenzoylmethane derivative inhibits lipopolysaccharide-induced NO production in mouse microglial cell line BV-2.

Abstract

Microglial activation has been suggested to play important roles in various neurodegenerative diseases by phagocytosis and producing various factors such as nitric oxide (NO), proinflammatory cytokines. Excessive production of NO, as a consequence of increased inducible nitric oxide synthase (iNOS) in microglia, contributes to the neurodegeneration. During a search for compounds that regulate endoplasmic reticulum (ER) stress, a dibenzoylmethane derivative, 2,2'-dimethoxydibenzoylmethane (DBM 14-26) was identified as a novel neuroprotective agent (Takano et al., Am. J. Physiol. Cell Physiol. 293, C1884-1894, 2007). We previously reported in cultured astrocytes that DBM 14-26 protected hydrogen peroxide-induced cell death and inhibited lipopolysaccharide (LPS)-induced NO production (Takano et al., J. Neurosci. Res. 89, 955-965, 2011). In the present study, we assessed the effects of DBM 14-26 on microglia using the mouse cell line BV-2 and found that DBM 14-26 inhibited LPS-induced iNOS expression and NO production also in microglia. DBM 14-26 also suppressed LPS-induced IL-1β expression. Conditioned medium of BV-2 cells stimulated by LPS significantly decreased cell viability of neuron (human neuroblastoma SH-SY5Y cells) compared with the absence of LPS. Conditioned medium of BV-2 cells stimulated by LPS in the presence of DBM 14-26 did not significantly decreased cell viability of neuron. These results indicate that microglial activation by LPS causes neuronal cell death and DBM 14-26 protect neuron through the inhibition of microglial activation. Functional regulation of microglia by DBM 14-26 could be a therapeutic candidate for the treatment of neurodegenerative diseases.

• Authors: Katsura Takano, Natsumi Ishida, Kenji Kawabe, Mitsuaki Moriyama, Satoshi Hibino, Tominari Choshi, Osamu Hori, Yoichi Nakamura
• Journal: Neurochemistry international (Neurochem Int) Vol. 119 Pg. 126-131 (10 2018) ISSN: 1872-9754 [Electronic] England
• PMID: 28390951 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Chalcones
• Cytokines
• Lipopolysaccharides
• Neuroprotective Agents
• dibenzoylmethane
• Nitric Oxide Synthase Type II

Topics

• Animals
• Astrocytes (drug effects, metabolism)
• Cell Line
• Chalcones (pharmacology)
• Cytokines (metabolism)
• Lipopolysaccharides (pharmacology)
• Microglia (drug effects, metabolism)
• Neuroprotective Agents (pharmacology)
• Nitric Oxide Synthase Type II (drug effects, metabolism)
• Signal Transduction (drug effects)