title: Dalesconols B inhibits lipopolysaccharide induced inflammation and suppresses NF-κB and p38/JNK activation in microglial cells.
abstract: Therapeutic strategies designed to inhibit the activation of microglia may lead to significant advancement in the treatment of most neurodegenerative diseases. Dalesconols B, also termed as TL2, is a newly found polyketide from a mantis-associated fungus and has been reported to exert potent immunosuppressive effects. In the present study, the anti-inflammatory effects of TL2 was investigated in lipopolysaccharide (LPS)-treated BV2 microglia and primary microglia cells. Our observations indicated that pretreatment with TL2 significantly inhibited the production of NO and PGE2 and suppressed the expression of pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), COX-2, TNF-α, IL-1β, IL-6, MCP-1 and MIP-1α in LPS-stimulated BV2 microglia. The nuclear translocation of NF-κB and the phosphorylation level of Akt, p38 and JNK MAP kinase pathways were also inhibited by TL2 in LPS-treated BV2 microglia. Moreover, TL2 also decreased Aβ-induced production of TNF-α, IL-1β and IL-6 in BV2 microglia. Additionally, TL2 protected primary cortical neurons against microglia-mediated neurotoxicity. Overall, our findings suggested that TL2 might be a promising therapeutic agent for alleviating the progress of neurodegenerative diseases associated with microglia activation.
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Han
authors.forename: Kailin
authors.initials: K
authors.lastname: Yin
authors.forename: Shenyang
authors.initials: S
authors.lastname: Zhang
authors.forename: Zhengzheng
authors.initials: Z
authors.lastname: Wu
authors.forename: Chunlin
authors.initials: C
authors.lastname: Wang
authors.forename: Qinxiu
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Pan
authors.forename: Beilei
authors.initials: B
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Renxiang
authors.initials: R
authors.lastname: Tan
authors.forename: Yun
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases