Gal-3BP Negatively Regulates NF-κB Signaling by Inhibiting the Activation of TAK1

Galectin-3-binding protein (Gal-3BP) is a member of the family of scavenger receptor cysteine-rich (SRCR) domain-containing proteins, which are associated with the immune system. However, the functional roles and signaling mechanisms of Gal-3BP in host defense and the immune response remain largely...

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Main Authors: Chang-Soo Hong, Mi-Ra Park, Eun-Gene Sun, Wonyoung Choi, Jun-Eul Hwang, Woo-Kyun Bae, Joon Haeng Rhee, Sang-Hee Cho, Ik-Joo Chung
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-07-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2019.01760/full
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author Chang-Soo Hong
Mi-Ra Park
Eun-Gene Sun
Wonyoung Choi
Jun-Eul Hwang
Woo-Kyun Bae
Woo-Kyun Bae
Joon Haeng Rhee
Sang-Hee Cho
Ik-Joo Chung
Ik-Joo Chung
author_facet Chang-Soo Hong
Mi-Ra Park
Eun-Gene Sun
Wonyoung Choi
Jun-Eul Hwang
Woo-Kyun Bae
Woo-Kyun Bae
Joon Haeng Rhee
Sang-Hee Cho
Ik-Joo Chung
Ik-Joo Chung
author_sort Chang-Soo Hong
collection DOAJ
description Galectin-3-binding protein (Gal-3BP) is a member of the family of scavenger receptor cysteine-rich (SRCR) domain-containing proteins, which are associated with the immune system. However, the functional roles and signaling mechanisms of Gal-3BP in host defense and the immune response remain largely unknown. Here, we identified cellular Gal-3BP as a negative regulator of NF-κB activation and proinflammatory cytokine production in lipopolysaccharide (LPS)-stimulated murine embryonic fibroblasts (MEFs). Furthermore, cellular Gal-3BP interacted with transforming growth factor β-activated kinase 1 (TAK1), a crucial mediator of NF-κB activation in response to cellular stress. Gal-3BP inhibited the phosphorylation of TAK1, leading to suppression of its kinase activity and reduced protein stability. In vivo we found that Lgals3BP deficiency in mice enhanced LPS-induced proinflammatory cytokine release and rendered mice more sensitive to LPS-induced endotoxin shock. Overall, these results suggest that Gal-3BP is a novel suppressor of TAK1-dependent NF-κB activation that may have potential in the prevention and treatment of inflammatory diseases.
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spelling doaj.art-bc52bce0c6084c24b0928b61329b90ec2022-12-22T02:18:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-07-011010.3389/fimmu.2019.01760465160Gal-3BP Negatively Regulates NF-κB Signaling by Inhibiting the Activation of TAK1Chang-Soo Hong0Mi-Ra Park1Eun-Gene Sun2Wonyoung Choi3Jun-Eul Hwang4Woo-Kyun Bae5Woo-Kyun Bae6Joon Haeng Rhee7Sang-Hee Cho8Ik-Joo Chung9Ik-Joo Chung10Department of Internal Medicine, Chonnam National University Medical School, Hwasun, South KoreaDepartment of Internal Medicine, Chonnam National University Medical School, Hwasun, South KoreaDepartment of Internal Medicine, Chonnam National University Medical School, Hwasun, South KoreaDepartment of Internal Medicine, Chonnam National University Medical School, Hwasun, South KoreaDepartment of Internal Medicine, Chonnam National University Medical School, Hwasun, South KoreaDepartment of Internal Medicine, Chonnam National University Medical School, Hwasun, South KoreaCombinatorial Tumor Immunotherapy MRC, Clinical Vaccine R&D Center and Department of Microbiology, Chonnam National University Medical School, Hwasun, South KoreaCombinatorial Tumor Immunotherapy MRC, Clinical Vaccine R&D Center and Department of Microbiology, Chonnam National University Medical School, Hwasun, South KoreaDepartment of Internal Medicine, Chonnam National University Medical School, Hwasun, South KoreaDepartment of Internal Medicine, Chonnam National University Medical School, Hwasun, South KoreaCombinatorial Tumor Immunotherapy MRC, Clinical Vaccine R&D Center and Department of Microbiology, Chonnam National University Medical School, Hwasun, South KoreaGalectin-3-binding protein (Gal-3BP) is a member of the family of scavenger receptor cysteine-rich (SRCR) domain-containing proteins, which are associated with the immune system. However, the functional roles and signaling mechanisms of Gal-3BP in host defense and the immune response remain largely unknown. Here, we identified cellular Gal-3BP as a negative regulator of NF-κB activation and proinflammatory cytokine production in lipopolysaccharide (LPS)-stimulated murine embryonic fibroblasts (MEFs). Furthermore, cellular Gal-3BP interacted with transforming growth factor β-activated kinase 1 (TAK1), a crucial mediator of NF-κB activation in response to cellular stress. Gal-3BP inhibited the phosphorylation of TAK1, leading to suppression of its kinase activity and reduced protein stability. In vivo we found that Lgals3BP deficiency in mice enhanced LPS-induced proinflammatory cytokine release and rendered mice more sensitive to LPS-induced endotoxin shock. Overall, these results suggest that Gal-3BP is a novel suppressor of TAK1-dependent NF-κB activation that may have potential in the prevention and treatment of inflammatory diseases.https://www.frontiersin.org/article/10.3389/fimmu.2019.01760/fullGal-3BPTAK1NF-κBproinflammatory cytokinelipopolysaccharide
spellingShingle Chang-Soo Hong
Mi-Ra Park
Eun-Gene Sun
Wonyoung Choi
Jun-Eul Hwang
Woo-Kyun Bae
Woo-Kyun Bae
Joon Haeng Rhee
Sang-Hee Cho
Ik-Joo Chung
Ik-Joo Chung
Gal-3BP Negatively Regulates NF-κB Signaling by Inhibiting the Activation of TAK1
Frontiers in Immunology
Gal-3BP
TAK1
NF-κB
proinflammatory cytokine
lipopolysaccharide
title Gal-3BP Negatively Regulates NF-κB Signaling by Inhibiting the Activation of TAK1
title_full Gal-3BP Negatively Regulates NF-κB Signaling by Inhibiting the Activation of TAK1
title_fullStr Gal-3BP Negatively Regulates NF-κB Signaling by Inhibiting the Activation of TAK1
title_full_unstemmed Gal-3BP Negatively Regulates NF-κB Signaling by Inhibiting the Activation of TAK1
title_short Gal-3BP Negatively Regulates NF-κB Signaling by Inhibiting the Activation of TAK1
title_sort gal 3bp negatively regulates nf κb signaling by inhibiting the activation of tak1
topic Gal-3BP
TAK1
NF-κB
proinflammatory cytokine
lipopolysaccharide
url https://www.frontiersin.org/article/10.3389/fimmu.2019.01760/full
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