title: Subanesthetic isoflurane reduces zymosan-induced inflammation in murine Kupffer cells by inhibiting ROS-activated p38 MAPK/NF-κB signaling.
abstract: Volatile anesthetic isoflurane (ISO) has immunomodulatory effects. The fungal component zymosan (ZY) induces inflammation through toll-like receptor 2 or dectin-1 signaling. We investigated the molecular actions of subanesthetic (0.7%) ISO against ZY-induced inflammatory activation in murine Kupffer cells (KCs), which are known as the resident macrophages within the liver. We observed that ISO reduced ZY-induced cyclooxygenase 2 upregulation and prostaglandin E2 release, as determined by western blot and radioimmunoassay, respectively. ISO also reduced the production of tumor necrosis factor-α, interleukin-1β, IL-6, high-mobility group box-1, macrophage inflammatory protein-1α, macrophage inflammatory protein-2, and monocyte chemoattractant protein-1 as assessed by enzyme-linked immunosorbent assays. ISO blocked the ZY-induced nuclear translocation and DNA-binding activity of nuclear factor- (NF)-κB p65. Moreover, ISO attenuated ZY-induced p38 mitogen-activated protein kinase (MAPK) activation partly by scavenging reactive oxygen species (ROS); the interregulation that ROS activated p38 MAPK followed by NF-κB activation was crucial for the ZY-induced inflammatory responses in KCs. An in vivo study by peritoneal injection of ZY into BALB/C mice confirmed the anti-inflammatory properties of 0.7% ISO against ZY in KCs. These results suggest that ISO ameliorates ZY-induced inflammatory responses in murine KCs by inhibiting the interconnected ROS/p38 MAPK/NF-κB signaling pathways.
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Road, Xi'an, Shaanxi 710032, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Road, Xi'an, Shaanxi 710032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Road, Xi'an, Shaanxi 710032, China.
authors.forename: Nan-lin
authors.initials: NL
authors.lastname: Li
authors.affiliation: Institute of Anal-Colorectal Surgery, No. 150 Central Hospital of PLA, Luoyang, Henan 451000, China ; State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Jun-tang
authors.initials: JT
authors.lastname: Li
authors.affiliation: Centre of Material and Drug Supply, No. 150 Central Hospital of PLA, Luoyang, Henan 451000, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yu
authors.affiliation: Centre of Material and Drug Supply, No. 150 Central Hospital of PLA, Luoyang, Henan 451000, China.
authors.forename: Ya-li
authors.initials: YL
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, No. 150 Central Hospital of PLA, Luoyang, Henan 451000, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Road, Xi'an, Shaanxi 710032, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yi
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Road, Xi'an, Shaanxi 710032, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Road, Xi'an, Shaanxi 710032, China.
authors.forename: Jie-fang
authors.initials: JF
authors.lastname: Bian
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Road, Xi'an, Shaanxi 710032, China.
authors.forename: Jiang-hao
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Road, Xi'an, Shaanxi 710032, China.
authors.forename: Shi-fang
authors.initials: SF
authors.lastname: Yuan
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Road, Xi'an, Shaanxi 710032, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Road, Xi'an, Shaanxi 710032, China.
authors.forename: Yong-gang
authors.initials: YG
authors.lastname: Lv
authors.affiliation: Institute of Anal-Colorectal Surgery, No. 150 Central Hospital of PLA, Luoyang, Henan 451000, China.
authors.forename: Ning-ning
authors.initials: NN
authors.lastname: Liu
authors.affiliation: Institute of Anal-Colorectal Surgery, No. 150 Central Hospital of PLA, Luoyang, Henan 451000, China.
authors.forename: Xiao-shan
authors.initials: XS
authors.lastname: Zhu
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Road, Xi'an, Shaanxi 710032, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ling
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, No. 15 Changle West Road, Xi'an, Shaanxi 710032, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yun
mesh_terms: D000777:Anesthetics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control; D007530:Isoflurane / Q000494:pharmacology* / Q000627:therapeutic use; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D015054:Zymosan / Q000633:toxicity; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000777:Anesthetics; D018925:Chemokines; D016207:Cytokines; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D015054:Zymosan; D007530:Isoflurane; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases