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Macrophage Liver Kinase B1 Interacts with IKKβ and Inhibits Inflammatory Signaling in Response to LPS
Author(s) -
Liu Zhaoyu,
Zou Minghui
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.718.8
Subject(s) - lipopolysaccharide , inflammation , macrophage , kinase , phosphorylation , immune system , proinflammatory cytokine , innate immune system , microbiology and biotechnology , signal transduction , iκb kinase , cytokine , chemistry , biology , nf κb , immunology , biochemistry , in vitro
Liver Kinase B1 (LKB1), a serine/threonine ki nase, 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 lipopolysaccharide (LPS). LPS‐induced pro‐inflammatory cytokines and pro‐inflammatory enzymes were monitored in bone marrow‐derived macrophages (BMDMs) 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 BMDMs from LKB1 KO than those from wild type mice. Consistently, LPS‐induced higher levels of NF‐κB activation in LKB1 deficient macrophages than the wild type. Further, LPS stimulation significantly increased LKB1 phosphorylation at serine 428, which promoted its binding to 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 those of control mice. We conclude that LKB1 inhibits LPS‐induced NF‐κB activation in macrophages.