title: 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.affiliation: Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan. Electronic address: takano@vet.osakafu-u.ac.jp.
authors.forename: Katsura
authors.initials: K
authors.lastname: Takano
authors.affiliation: Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Ishida
authors.affiliation: Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawabe
authors.affiliation: Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Moriyama
authors.affiliation: Fukuyama University, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama, Hiroshima, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hibino
authors.affiliation: Fukuyama University, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama, Hiroshima, Japan.
authors.forename: Tominari
authors.initials: T
authors.lastname: Choshi
authors.affiliation: Department of Neuroanatomy, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Hori
authors.affiliation: Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D047188:Chalcones / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047188:Chalcones; D016207:Cytokines; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; C061481:dibenzoylmethane; D052247:Nitric Oxide Synthase Type II
keywords: Cytokines; Dibenzoylmethane; Microglia; NO production