PMID- 36865477 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230304 IS - 2405-8440 (Print) IS - 2405-8440 (Electronic) IS - 2405-8440 (Linking) VI - 9 IP - 2 DP - 2023 Feb TI - Forsythiaside A prevents zymosan A-induced cell migration in neutrophil-differentiated HL-60 cells via PD-1/PD-L1 pathway. PG - e13490 LID - 10.1016/j.heliyon.2023.e13490 [doi] LID - e13490 AB - 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-alpha), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and interferon-gamma (IFN-gamma) 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. CI - (c) 2023 The Authors. FAU - Zhang, Xinyu AU - Zhang X AD - Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Li, Aiyun AU - Li A AD - School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Xu, Yue AU - Xu Y AD - School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Lan, Jinshuai AU - Lan J AD - Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Liu, Yun AU - Liu Y AD - Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Li, Ling AU - Li L AD - Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Kang, Ping AU - Kang P AD - School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Zhang, Tong AU - Zhang T AD - Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, China. LA - eng PT - Journal Article DEP - 20230208 PL - England TA - Heliyon JT - Heliyon JID - 101672560 PMC - PMC9970906 OTO - NOTNLM OT - Forsythiaside A OT - Immunosuppression OT - Inflammation OT - Neutrophils OT - PD-L1 COIS- The authors declare no competing interests. EDAT- 2023/03/04 06:00 MHDA- 2023/03/04 06:01 PMCR- 2023/02/08 CRDT- 2023/03/03 02:31 PHST- 2022/06/10 00:00 [received] PHST- 2023/01/09 00:00 [revised] PHST- 2023/01/31 00:00 [accepted] PHST- 2023/03/03 02:31 [entrez] PHST- 2023/03/04 06:00 [pubmed] PHST- 2023/03/04 06:01 [medline] PHST- 2023/02/08 00:00 [pmc-release] AID - S2405-8440(23)00697-7 [pii] AID - e13490 [pii] AID - 10.1016/j.heliyon.2023.e13490 [doi] PST - epublish SO - Heliyon. 2023 Feb 8;9(2):e13490. doi: 10.1016/j.heliyon.2023.e13490. eCollection 2023 Feb.