Mycoepoxydiene inhibits activation of BV2 microglia stimulated by lipopolysaccharide through suppressing NF-κB, ERK 1/2 and toll-like receptor pathways.
Mycoepoxydiene (MED) is a polyketide isolated from the marine fungal Diaporthe sp. HLY-1 associated with mangroves. Although MED has been shown to have various biological effects such as antimicrobial, anti-cancer, and anti-inflammatory activities, its activities and cellular mechanisms during microglial activation have yet to be elucidated. In the present study, we assessed the anti-inflammatory effect of MED on the production of inflammatory mediators in lipopolysaccharide (LPS)-stimulated murine BV2 microglia. MED significantly inhibited LPS-induced production of pro-inflammatory mediators such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interferon-γ (INF-γ), and nitric oxide (NO), whereas it increased anti-inflammatory interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) production in BV2 microglia in a concentration-dependent manner without causing cytotoxicity. Moreover, MED suppressed NF-κB activation by blocking IkappaB-α (IκB-α) degradation and inhibited the phosphorylation of ERK 1/2 and toll-like receptor 4 (TLR4) expression, but had no effect on the phosphorylation of JNK, and p38. Our results demonstrate that the inhibitory and promotion effect of MED on LPS-stimulated inflammatory mediators and anti-inflammatory factor production in BV2 microglia is associated with the suppression of the NF-κB, ERK1/2 and TLR signaling pathways. Therefore, MED may have therapeutic potential for neurodegenerative diseases by inhibiting inflammatory mediators and enhancing anti-inflammatory factor production in activated microglia.
Department of Nuclear Medicine & Minnan PET Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.
Xinhui
X
Su
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
Qiang
Q
Chen
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
Wenbo
W
Chen
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
Tenghui
T
Chen
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
Wenjiao
W
Li
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
Yang
Y
Li
Department of Nuclear Medicine & Minnan PET Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.
Xiaofeng
X
Dou
Department of Nuclear Medicine & Minnan PET Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.
Yafei
Y
Zhang
School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.
Yuemao
Y
Shen
Department of Nuclear Medicine & Minnan PET Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China. Electronic address: wuhua1025@163.com.
Hua
H
Wu
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China. Electronic address: cdyu@xmu.edu.cn.
Chundong
C
Yu
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology; D009569:Nitric Oxide / Q000276:immunology; D011753:Pyrones / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000276:immunology
D000893:Anti-Inflammatory Agents; D001952:Bridged-Ring Compounds; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011753:Pyrones; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C476085:mycoepoxydiene; D009569:Nitric Oxide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
Microglia; Mitogen-activated protein kinase; Mycoepoxydiene; NF-κB; Pro-inflammatory mediators; Toll-like receptor