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

Frontiers in Immunology

Woo-Kyun Bae¹  Sang-Hee Cho¹  Joon Haeng Rhee²  Mi-Ra Park³  Eun-Gene Sun³  Ik-Joo Chung³  Chang-Soo Hong³  Wonyoung Choi³  Jun-Eul Hwang³ 

[1] Combinatorial Tumor Immunotherapy MRC, Clinical Vaccine R&D Center and Department of Microbiology, Chonnam National University Medical School, Hwasun, South Korea;Department of Internal Medicine, Chonnam National University Medical School, Hwasun, South Korea;

关键词: Gal-3BP;    TAK1;    NF-κB;    proinflammatory cytokine;    lipopolysaccharide;   

DOI  :  10.3389/fimmu.2019.01760

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown