title: Lipoxin A4 inhibits the production of proinflammatory cytokines induced by β-amyloid in vitro and in vivo.
abstract: Studies increasingly indicate that inflammation induced by β-amyloid (Aβ) contributes to the progression of Alzheimer's disease (AD). How to inhibit the enhanced production of proinflammatory cytokines stimulated by Aβ is an important research subject for the treatment of AD. In this study, we investigated the inhibitory effect and the molecular mechanism of the lipoxin A(4) (LXA(4)) on the production of interleukin-1β (IL-1β) and tumor necrosis factorα (TNFα) induced by β-amyloid in the cortex and hippocampus of mice, and in Aβ-stimulated BV2 cells, a mouse microglial cell line. LXA(4) down-regulated the protein expression of IL-1β and TNFα, attenuated the gene expressions of IL-1β and TNFα, inhibited the degradation of IκBα, inhibited translocation of NF-κB p65 subunit into the nucleus induced by β-amyloid in the cortex and hippocampus of mice, and in Aβ-stimulated BV2 cells, and the inhibitory effects were dose dependently elevated. Our findings suggest that LXA(4) inhibits the production of IL-1β and TNFα induced by β-amyloid in the cortex and hippocampus of mice, and in BV2 microglial cells via the NF-κB signal pathway.
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Aitao
authors.initials: A
authors.lastname: Wang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Min
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Xiong
authors.forename: Qiuyue
authors.initials: Q
authors.lastname: Yan
authors.forename: Jinping
authors.initials: J
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Suming
authors.initials: S
authors.lastname: Zhang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D044045:Lipoxins / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D044045:Lipoxins; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C040527:lipoxin A4