Department of Internal Medicine, Chonnam National University Medical School, Hwasun, South Korea.
Combinatorial Tumor Immunotherapy MRC, Clinical Vaccine R&D Center and Department of Microbiology, Chonnam National University Medical School, Hwasun, South Korea.
Front Immunol. 2019 Jul 26;10:1760. doi: 10.3389/fimmu.2019.01760. eCollection 2019.
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. we found that 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.
半乳糖凝集素-3 结合蛋白（Gal-3BP）是清道夫受体富含胱氨酸域（SRCR）家族蛋白的成员，与免疫系统有关。然而，Gal-3BP 在宿主防御和免疫反应中的功能作用和信号机制在很大程度上尚不清楚。在这里，我们鉴定了细胞 Gal-3BP 是脂多糖（LPS）刺激的鼠胚胎成纤维细胞（MEFs）中 NF-κB 激活和促炎细胞因子产生的负调节剂。此外，细胞 Gal-3BP 与转化生长因子β激活激酶 1（TAK1）相互作用，TAK1 是细胞应激反应中 NF-κB 激活的关键介质。Gal-3BP 抑制了 TAK1 的磷酸化，从而抑制了其激酶活性和降低了蛋白稳定性。我们发现，小鼠中 Gal-3BP 的缺乏增强了 LPS 诱导的促炎细胞因子释放，并使小鼠对 LPS 诱导的内毒素休克更加敏感。总体而言，这些结果表明 Gal-3BP 是 TAK1 依赖性 NF-κB 激活的新型抑制剂，可能在炎症性疾病的预防和治疗中有一定的应用前景。
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