title: AAL exacerbates pro-inflammatory response in macrophages by regulating Mincle/Syk/Card9 signaling along with the Nlrp3 inflammasome assembly.
abstract: Previously, we demonstrated that Agrocybe aegerita lectin (AAL), a galectin isolated from edible mushroom Agrocybe aegerita, exerts potent anti-tumor activity, while the mechanisms by which AAL suppresses tumor growth are yet to be elucidated. Here, we conducted studies with focus for its impact on the cecal ligation and puncture (CLP)-induced innate immune response. Administration of AAL significantly exacerbated the severity of CLP-induced septic shock as manifested the increased lethality. AAL promoted inflammatory cytokine production by preferentially regulating macrophage activation and recruitment. Mechanistic studies revealed that AAL likely targets macrophages through receptor Mincle to activate Syk/Card9 signaling, which then couples to the Nlrp3 inflammasome assembly. It was further noted that AAL markedly promotes H3K4 di- and trimethylation, by which it enhances Hmgb1 expression. Specifically, AAL induced macrophages secretion of copious amount of Hmgb1 as manifested the Hmgb1 cytoplasmic translocation along with the detection of extracellular Hmgb1. AAL also stimulated a significant increase for nuclear Hmgb1, which then formed a complex with RelA, and thereby enhancing NF-κB transcriptional activity. Together, our data suggest that AAL may possess important pharmaceutical properties in the regulation of innate immune response.
authors.affiliation: The Center for Biomedical Research, Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology 1095 Jiefang Ave., Wuhan 430030, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: The Center for Biomedical Research, Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology 1095 Jiefang Ave., Wuhan 430030, China.
authors.forename: Long
authors.initials: L
authors.lastname: He
authors.affiliation: The Center for Biomedical Research, Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology 1095 Jiefang Ave., Wuhan 430030, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Hu
authors.affiliation: The Center for Biomedical Research, Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology 1095 Jiefang Ave., Wuhan 430030, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Center for Biomedical Research, Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology 1095 Jiefang Ave., Wuhan 430030, China.
authors.forename: Qiaohong
authors.initials: Q
authors.lastname: Lai
authors.affiliation: The Center for Biomedical Research, Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology 1095 Jiefang Ave., Wuhan 430030, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: The Center for Biomedical Research, Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology 1095 Jiefang Ave., Wuhan 430030, China.
authors.forename: Qilin
authors.initials: Q
authors.lastname: Yu
authors.affiliation: The Center for Biomedical Research, Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology 1095 Jiefang Ave., Wuhan 430030, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: The Center for Biomedical Research, Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology 1095 Jiefang Ave., Wuhan 430030, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiong
authors.affiliation: The Center for Biomedical Research, Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology 1095 Jiefang Ave., Wuhan 430030, China.
authors.forename: Sakine
authors.initials: S
authors.lastname: Simsekyilmaz
authors.affiliation: Department of Infectious Disease, Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology 1095 Jiefang Ave., Wuhan 430030, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ning
authors.affiliation: Department of Emergency Medicine, Institute of Emergency Medicine and Rare Diseases, The Second Xiangya Hospital, Central South University Changsha, China.
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Emergency Medicine, Institute of Emergency Medicine and Rare Diseases, The Second Xiangya Hospital, Central South University Changsha, China.
authors.forename: Dongshan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Emergency Medicine, Institute of Emergency Medicine and Rare Diseases, The Second Xiangya Hospital, Central South University Changsha, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Emergency Medicine, Institute of Emergency Medicine and Rare Diseases, The Second Xiangya Hospital, Central South University Changsha, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Xiang
authors.affiliation: Diabetes Center, Key Laboratory of Diabetes Immunology, The Second Xiangya Hospital, Central South University Changsha, China.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: College of Life Sciences, Wuhan University Wuhan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.affiliation: The Center for Biomedical Research, Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology 1095 Jiefang Ave., Wuhan 430030, China.
authors.forename: Cong-Yi
authors.initials: CY
authors.lastname: Wang
keywords: AAL; CLP; Hmgb1; NF-κB; Nlrp3 inflammasome; innate immunity; methylation; mincle; septic shock