The anti‐TLR4 monoclonal antibody Sa15‐21 enhances inflammatory cytokine production in LPS‐stimulated macrophages
The anti‐TLR4 monoclonal antibody Sa15‐21 enhances inflammatory cytokine production in LPS‐stimulated macrophages
复制标题
抗 TLR4 单克隆抗体 Sa15-21 增强 LPS 刺激的巨噬细胞中炎症细胞因子的产生
DOI：
10.1002/1873-3468.14619
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发表时间：
2023
期刊：
影响因子：
3.5
通讯作者：
Akashi‐Takamura Sachiko
中科院分区：
文献类型：
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作者：
Chowdhury Sajid Iftekhar;Inui Masanori;Yamazaki Tatsuya;Tomono Susumu;Takagi Hidekazu;Biswas Mrityunjoy;Saitoh Shin‐Ichiroh;Miyake Kensuke;Akashi‐Takamura Sachiko
Sa 15 - 21是一种抗小鼠Toll样受体（TLR）4的单克隆抗体，可保护小鼠免受脂多糖（LPS）/D-半乳糖胺诱导的急性致死性肝炎。在此，我们研究了巨噬细胞中Sa 15 - 21-介导的TLR 4信号调节的分子机制。结果表明，Sa 15 - 21可增强LPS刺激的巨噬细胞中促炎细胞因子的产生，并减弱抗炎细胞因子的产生。Western blotting分析显示，Sa 15 - 21预处理对LPS刺激的巨噬细胞中的NF-κB和MAPK信号传导没有影响;然而，单独Sa 15 - 21处理导致NF-κB和MAPK信号传导的弱活化和延迟活化，对促炎细胞因子产生没有任何影响。相反，Sa 15 - 21不能诱导干扰素调节因子3的活化。综上所述，我们的结果表明，Sa 15 - 21通过TLR信号转导使巨噬细胞敏感以促进炎症反应。
Sa15‐21, a monoclonal antibody against mouse Toll‐like receptor (TLR) 4, can protect mice from lipopolysaccharide (LPS)/D‐galactosamine‐induced acute lethal hepatitis. Herein, we investigated the molecular mechanisms underlying Sa15‐21‐mediated regulation of TLR4 signaling in macrophages. Results showed that Sa15‐21 enhanced the production of proinflammatory cytokines and attenuated the production of anti‐inflammatory cytokines in LPS‐stimulated macrophages. Western blotting analysis revealed that Sa15‐21 pretreatment had no effect on NF‐κB and MAPK signaling in LPS‐stimulated macrophages; however, Sa15‐21 treatment alone led to a weak and delayed activation of NF‐κB and MAPK signaling without any effect on proinflammatory cytokine production. By contrast, Sa15‐21 failed to induce the activation of interferon regulatory factor 3. Taken together, our results indicate that Sa15‐21 sensitizes macrophages to facilitate the inflammatory response via TLR signaling.