Forsythiaside A prevents zymosan A-induced cell migration in neutrophil-differentiated HL-60 cells via PD-1/PD-L1 pathway

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 Forsythia suspensa (Thunb.) Vahl, provides a very significant...

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Main Authors: Xinyu Zhang, Aiyun Li, Yue Xu, Jinshuai Lan, Yun Liu, Ling Li, Ping Kang, Tong Zhang
Format: Article
Language:English
Published: Elsevier 2023-02-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844023006977
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author Xinyu Zhang
Aiyun Li
Yue Xu
Jinshuai Lan
Yun Liu
Ling Li
Ping Kang
Tong Zhang
author_facet Xinyu Zhang
Aiyun Li
Yue Xu
Jinshuai Lan
Yun Liu
Ling Li
Ping Kang
Tong Zhang
author_sort Xinyu Zhang
collection DOAJ
description 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 Forsythia suspensa (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 in vitro, and this action appeared to be mediated via PD-1/PD-L1 depended JNK and p38 MAPK pathways. In vivo, 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.
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spelling doaj.art-3ec287968606426ebb5899f99ae8218c2023-03-02T05:01:49ZengElsevierHeliyon2405-84402023-02-0192e13490Forsythiaside A prevents zymosan A-induced cell migration in neutrophil-differentiated HL-60 cells via PD-1/PD-L1 pathwayXinyu Zhang0Aiyun Li1Yue Xu2Jinshuai Lan3Yun Liu4Ling Li5Ping Kang6Tong Zhang7Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaExperiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaExperiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaExperiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Corresponding author. Headmaster’s Office, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China.Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Corresponding author. School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China.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 Forsythia suspensa (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 in vitro, and this action appeared to be mediated via PD-1/PD-L1 depended JNK and p38 MAPK pathways. In vivo, 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.http://www.sciencedirect.com/science/article/pii/S2405844023006977Forsythiaside APD-L1NeutrophilsInflammationImmunosuppression
spellingShingle Xinyu Zhang
Aiyun Li
Yue Xu
Jinshuai Lan
Yun Liu
Ling Li
Ping Kang
Tong Zhang
Forsythiaside A prevents zymosan A-induced cell migration in neutrophil-differentiated HL-60 cells via PD-1/PD-L1 pathway
Heliyon
Forsythiaside A
PD-L1
Neutrophils
Inflammation
Immunosuppression
title Forsythiaside A prevents zymosan A-induced cell migration in neutrophil-differentiated HL-60 cells via PD-1/PD-L1 pathway
title_full Forsythiaside A prevents zymosan A-induced cell migration in neutrophil-differentiated HL-60 cells via PD-1/PD-L1 pathway
title_fullStr Forsythiaside A prevents zymosan A-induced cell migration in neutrophil-differentiated HL-60 cells via PD-1/PD-L1 pathway
title_full_unstemmed Forsythiaside A prevents zymosan A-induced cell migration in neutrophil-differentiated HL-60 cells via PD-1/PD-L1 pathway
title_short Forsythiaside A prevents zymosan A-induced cell migration in neutrophil-differentiated HL-60 cells via PD-1/PD-L1 pathway
title_sort forsythiaside a prevents zymosan a induced cell migration in neutrophil differentiated hl 60 cells via pd 1 pd l1 pathway
topic Forsythiaside A
PD-L1
Neutrophils
Inflammation
Immunosuppression
url http://www.sciencedirect.com/science/article/pii/S2405844023006977
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