title: Liver kinase B1 suppresses lipopolysaccharide-induced nuclear factor κB (NF-κB) activation in macrophages.
abstract: Liver kinase B1 (LKB1), a serine/threonine kinase, is a tumor suppressor and metabolic regulator. Recent data suggest that LKB1 is essential in regulating homeostasis of hematopoietic cells and immune responses. However, its role in macrophages and innate immune system remains unclear. Here we report that macrophage LKB1 inhibits pro-inflammatory signaling in response to LPS. LPS-induced pro-inflammatory cytokines and pro-inflammatory enzymes were monitored in bone marrow-derived macrophages isolated from myeloid cell-specific LKB1 knock out mice and their wild type littermate control mice. LPS induced higher levels of pro-inflammatory cytokines and pro-inflammatory enzymes in bone marrow-derived macrophages from LKB1 KO than those from wild type mice. Consistently, LPS induced higher levels of NF-κB activation in LKB1-deficient macrophages than those in wild type. Further, LPS stimulation significantly increased LKB1 phosphorylation at serine 428, which promoted its binding to IκB kinaseβ (IKKβ), resulting in the inhibition of NF-κB. Finally, LPS injection caused higher levels of cytokine release and more severe tissue injury in the lung tissues of LKB1 KO mice than in those of control mice. We conclude that LKB1 inhibits LPS-induced NF-κB activation in macrophages.
authors.affiliation: From the Section of Molecular Medicine, Department of Medicine, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104.
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: From the Section of Molecular Medicine, Department of Medicine, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104.
authors.forename: Wencheng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: From the Section of Molecular Medicine, Department of Medicine, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104.
authors.forename: Miao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: From the Section of Molecular Medicine, Department of Medicine, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104.
authors.forename: Huaiping
authors.initials: H
authors.lastname: Zhu
authors.affiliation: From the Section of Molecular Medicine, Department of Medicine, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104.
authors.forename: Cate
authors.initials: C
authors.lastname: Moriasi
authors.affiliation: From the Section of Molecular Medicine, Department of Medicine, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104 mzou@ouhsc.edu.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Zou
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D004731:Endotoxins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation; D008070:Lipopolysaccharides / Q000737:chemistry; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012694:Serine / Q000737:chemistry; D015398:Signal Transduction
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012694:Serine; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D051550:I-kappa B Kinase; D055372:AMP-Activated Protein Kinases
keywords: Endotoxin; Inflammation; Lipopolysaccharide (LPS); Liver Kinase B1 (LKB1); Macrophage; Nuclear Factor Kappa B