Zhang Xinyu, Li Aiyun, Xu Yue, Lan Jinshuai, Liu Yun, Li Ling, Kang Ping, Zhang Tong
Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Heliyon. 2023 Feb 8;9(2):e13490. doi: 10.1016/j.heliyon.2023.e13490. eCollection 2023 Feb.
Neutrophils, which account for more than 80% of leukocyte, play an important role in resolution of inflammation. Immune checkpoint molecules could be potential biomarkers in immunosuppression. Forsythiaside A (FTA), a main constituent of (Thunb.) Vahl, provides a very significant anti-inflammatory activity. Here we defined the immunological mechanisms of FTA by taking programmed cell death-1 (PD-1)/programmed cell death-Ligand 1 (PD-L1) pathway into consideration. FTA could inhibited cell migration in HL-60-derived neutrophils , and this action appeared to be mediated via PD-1/PD-L1 depended JNK and p38 MAPK pathways. , FTA prevented PD-L1 neutrophils infiltration and reduced the levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and interferon-gamma (IFN-γ) after zymosan A-induced peritonitis. PD-1/PD-L1 inhibitor could abolish the suppression of FTA. The expression of inflammatory cytokines and chemokines were positively correlated with PD-L1. Molecular docking showed that FTA could bind to PD-L1. Taken together, FTA might prevent neutrophils infiltration to exert inflammation resolution through PD-1/PD-L1 pathway.
中性粒细胞占白细胞的80%以上，在炎症消退中起重要作用。免疫检查点分子可能是免疫抑制的潜在生物标志物。连翘酯苷A（FTA）是连翘（Thunb.）Vahl的主要成分，具有非常显著的抗炎活性。在这里，我们通过考虑程序性细胞死亡蛋白1（PD-1）/程序性细胞死亡配体1（PD-L1）途径来确定FTA的免疫机制。FTA可抑制HL-60来源的中性粒细胞的细胞迁移，且这种作用似乎是通过PD-1/PD-L1依赖的JNK和p38丝裂原活化蛋白激酶（MAPK）途径介导的。此外，FTA可防止PD-L1阳性中性粒细胞浸润，并降低酵母聚糖A诱导的腹膜炎后肿瘤坏死因子α（TNF-α）、白细胞介素-6（IL-6）、单核细胞趋化蛋白-1（MCP-1）和干扰素-γ（IFN-γ）的水平。PD-1/PD-L1抑制剂可消除FTA的抑制作用。炎性细胞因子和趋化因子的表达与PD-L1呈正相关。分子对接显示FTA可与PD-L1结合。综上所述，FTA可能通过PD-1/PD-L1途径阻止中性粒细胞浸润以发挥炎症消退作用。
