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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Frontiers Media S.A.
2019-07-01
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Series: | Frontiers in Immunology |
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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. |
first_indexed | 2024-04-14T01:57:28Z |
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id | doaj.art-bc52bce0c6084c24b0928b61329b90ec |
institution | Directory Open Access Journal |
issn | 1664-3224 |
language | English |
last_indexed | 2024-04-14T01:57:28Z |
publishDate | 2019-07-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Immunology |
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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