title: BHBA suppresses LPS-induced inflammation in BV-2 cells by inhibiting NF-κB activation.
abstract: β-Hydroxybutyric acid (BHBA) has neuroprotective effects, but the underlying molecular mechanisms are unclear. Microglial activation plays an important role in neurodegenerative diseases by producing several proinflammatory enzymes and proinflammatory cytokines. The current study investigates the potential mechanisms whereby BHBA affects the expression of potentially proinflammatory proteins by cultured murine microglial BV-2 cells stimulated with lipopolysaccharide (LPS). The results showed that BHBA significantly reduced LPS-induced protein and mRNA expression levels of iNOS, COX-2, TNF-α, IL-1β, and IL-6. Blocking of GPR109A by PTX resulted in a loss of this anti-inflammatory effect in BV-2 cells. Western blot analysis showed that BHBA reduced LPS-induced degradation of IκB-α and translocation of NF-κB, while no effect was observed on MAPKs phosphorylation. All results imply that BHBA significantly reduces levels of proinflammatory enzymes and proinflammatory cytokines by inhibition of the NF-κB signaling pathway but not MAPKs pathways, and GPR109A is essential to this function. Overall, these data suggest that BHBA has a potential as neuroprotective drug candidate in neurodegenerative diseases.
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Shou-Peng
authors.initials: SP
authors.lastname: Fu
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Su-Nan
authors.initials: SN
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China ; College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China.
authors.forename: Jian-Fa
authors.initials: JF
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Xie
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Xue
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Bing-Xu
authors.initials: BX
authors.lastname: Huang
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Qing-Kang
authors.initials: QK
authors.lastname: Lv
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Lian-Cheng
authors.initials: LC
authors.lastname: Lei
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Guo-Wen
authors.initials: GW
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Ju-Xiong
authors.initials: JX
authors.lastname: Liu
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha; D020155:3-Hydroxybutyric Acid