title: Berberine augments ATP-induced inflammasome activation in macrophages by enhancing AMPK signaling.
abstract: The isoquinoline alkaloid berberine possesses many pharmacological activities including antibacterial infection. Although the direct bactericidal effect of berberine has been documented, its influence on the antibacterial functions of macrophages is largely unknown. As inflammasome activation in macrophages is important for the defense against bacterial infection, we aimed to investigate the influence of berberine on inflammasome activation in murine macrophages. Our results showed that berberine significantly increased ATP-induced inflammasome activation as reflected by enhanced pyroptosis as well as increased release of caspase-1p10 and mature interleukin-1β (IL-1β) in macrophages. Such effects of berberine could be suppressed by AMP-activated protein kinase (AMPK) inhibitor compound C or by knockdown of AMPKα expression, indicating the involvement of AMPK signaling in this process. In line with increased IL-1β release, the ability of macrophages to kill engulfed bacteria was also intensified by berberine. This was corroborated by the in vivo finding that the peritoneal live bacterial load was decreased by berberine treatment. Moreover, berberine administration significantly improved survival of bacterial infected mice, concomitant with increased IL-1β levels and elevated neutrophil recruitment in the peritoneal cavity. Collectively, these data suggested that berberine could enhance bacterial killing by augmenting inflammasome activation in macrophages through AMPK signaling.
authors.affiliation: Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou, China.
authors.forename: Chen-Guang
authors.initials: CG
authors.lastname: Li
authors.affiliation: Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou, China.
authors.forename: Yan-Yun
authors.initials: YY
authors.lastname: Jing
authors.affiliation: Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, China.
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Xu
authors.affiliation: Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou, China.
authors.forename: Yi-Dan
authors.initials: YD
authors.lastname: Liang
authors.affiliation: Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou, China.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Wei
authors.affiliation: Department of Nephrology, the First Affiliated Hospital of Jinan University, Guangzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Fetal Medicine, the First Affiliated Hospital of Jinan University, Guangzhou, China.
authors.forename: Qing-Bing
authors.initials: QB
authors.lastname: Zha
authors.affiliation: Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou, China.
authors.forename: Dong-Yun
authors.initials: DY
authors.lastname: Ouyang
authors.affiliation: Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou, China.
authors.forename: Xian-Hui
authors.initials: XH
authors.lastname: He
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D001599:Berberine / Q000494:pharmacology*; D005260:Female; D058847:Inflammasomes / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology; D051379:Mice; D050296:Microbial Viability / Q000276:immunology; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000382:microbiology
chemical_list: D058847:Inflammasomes; D001599:Berberine; D000255:Adenosine Triphosphate
keywords: AMP-activated protein kinase (AMPK); Immune response; Immunity; Immunology and Microbiology Section; antibacterial infection; berberine; inflammasome; macrophages