Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Zhang X

PROVIDER: S-EPMC9970906 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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

Zhang Xinyu X Li Aiyun A Xu Yue Y Lan Jinshuai J Liu Yun Y Li Ling L Kang Ping P Zhang Tong T

Heliyon 20230208 2

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 <i>Forsythia suspensa</i> (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 c ...[more]

PMID: 36865477

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Project description:Toll-like receptor 2 (TLR2) is an important sensor for innate immune cells, including neutrophils, for the recognition of pathogen infection. Lipoteichoic acid (LTA), a cell wall component of gram-positive bacteria, is a TLR2 ligand. LTA-induced TLR2 signaling pathways are well established in neutrophils. However, experimental studies regarding transcriptional regulation and the molecular mechanisms in primary human neutrophils are limited due to their short lifespan. The promyelocytic leukemia cell line, HL-60, can differentiate into a neutrophil-like phenotype following treatment with dimethyl sulfoxide. The aim of the present study was to investigate whether differentiated HL-60 (dHL-60) cells induced a similar gene expression profile upon LTA treatment as that previously determined for primary human neutrophils. After 4 or 24 h of Staphylococcus aureus LTA treatment, undifferentiated HL-60 (uHL-60) and dHL-60 cells were collected for RNA sequencing. The results demonstrated that hundreds of identical differentially expressed genes (DEGs) were observed in 1 and 10 µg/ml LTA-treated dHL-60 cells following 4 and 24 h of incubation, while almost no DEGs between LTA-treated HL-60 and dHL-60 cells were observed. Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses (KEGG), it was noted that the pathways of shared DEGs between the 1 and 10 µg/ml LTA-treated dHL-60 cells at both time points were significantly enriched in immune and inflammatory response-related pathways, such as cellular response to tumor necrosis factor, interleukin-1, interferon γ, neutrophil chemotaxis, the NF-κB signaling pathway and the Toll-like receptor signaling pathway. In addition, when comparing the effect of 1 and 10 µg/ml LTA treatment on dHL60 cells, it was found that all enriched GO and KEGG pathways were associated with the TLR signaling pathways of neutrophils. The results of the present study provided important information for the implementation of mRNA profiling in LTA-treated dHL-60 cells and may indicate the feasibility of using dHL-60 cells as a research model for TLR2 signaling in human neutrophils.

Dataset Information

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

Publications

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

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