title: Surfactin inducing mitochondria-dependent ROS to activate MAPKs, NF-κB and inflammasomes in macrophages for adjuvant activity.
abstract: Surfactin, a natural lipopeptide, can be used both as parenteral and non-parenteral adjuvant for eliciting immune response. However, the mechanisms that confer its adjuvant properties have not been fully explored. By staining with NHS-Rhodamine B labeled surfactin and Mito-Tracker Green, we found surfactin could penetrate into macrophages to bind with mitochondria, following induce ROS that could be inhibited by mitochondria-dependent ROS inhibitor. ROS enhanced p38 MAPK and JNK expression, as well their phorsphorylation, following activated NF-κB nuclear translocation in macrophages that was obviously inhibited by mitochondria-dependent ROS inhibitor. However, inhibition of ROS production only weakened p38 MAPK and JNK expression, but not their phosphorylation in macrophages. As a result, surfaction could activate NF-κB to release TNF-α by the mitochondria-dependent ROS signalling pathway. ROS also induced macrophages apoptosis to release endogenous danger signals, following activated inflammasomes of NLRP1, NLRP3, IPAF and AIM2 in vitro and only NLRP1 in vivo, as well caspase-1 and IL-1 in macrophages, which were significantly inhibited by pre-treatment with ROS inhibitors. Collectively, surfactin as a kind of non-pathogen-associated molecular patterns, modulates host innate immunity by multiple signalling pathways, including induction of mitochondria-dependent ROS, activating MAPKs and NF-κB, and inducing cell apoptosis to realease endogenous danger signals for activation of inflammasomes.
authors.affiliation: College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.|Guilin Medical University, No. 1 Zhiyuan Road, Lingui District, Guilin, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gan
authors.affiliation: School of Pharmacy, Yancheng Teachers' University, Xiwang Road, Yancheng, 224051, China.
authors.forename: Zhenqiu
authors.initials: Z
authors.lastname: Gao
authors.affiliation: College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Xiuyun
authors.initials: X
authors.lastname: Zhao
authors.affiliation: College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.|Biomedical Center, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Gaofu
authors.initials: G
authors.lastname: Qi
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism; D000818:Animals; D058847:Inflammasomes / Q000378:metabolism*; D055666:Lipopeptides / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D058847:Inflammasomes; D055666:Lipopeptides; D016328:NF-kappa B; D010456:Peptides, Cyclic; D017382:Reactive Oxygen Species; C009365:surfactin peptide; D020928:Mitogen-Activated Protein Kinases