title: Methane limit LPS-induced NF-κB/MAPKs signal in macrophages and suppress immune response in mice by enhancing PI3K/AKT/GSK-3β-mediated IL-10 expression.
abstract: Inflammatory diseases such as sepsis and autoimmune colitis, characterized by an overwhelming activation of the immune system and the counteracting anti-inflammatory response, remain a major health problem in worldwide. Emerging evidence suggests that methane have a protective effect on many animal models, like ischaemia reperfusion injury and diabetes-associated diseases. Whether methane could modulating inflammatory diseases remains largely unknown. Here we show that methane-rich saline (MS) ip treatment (16 ml/kg) alleviated endotoxin shock, bacteria-induced sepsis and dextran-sulfate-sodium-induced colitis in mice via decreased production of TNF-α and IL-6. In MS-treated macrophages, LPS-induced activation of NF-κb/MAPKs was attenuated. Interestingly, MS treatment significantly elevated the levels of IL-10 both in vitro and in vivo. Neutralization of IL-10 abrogated the therapeutic effect of MS. Moreover, anti-IL10 blockade partially restored the MS-mediated attenuation of NF-κb/MAPKs phosphorylation. We further found that MS resulted in markedly enhanced phosphorylation of GSK-3β and AKT, which both mediate the release of Il-10. Additionally, inhibition of PI3K attenuated MS-mediated p-GSK-3β and IL-10 production and reversed the suppressed activation of NF-κb/ MAPKs in response to LPS. Our results reveal a novel effect and mechanisms of methane and support the potential value of MS as a therapeutic approach in innate inflammatory diseases.
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China (mainland).|Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, 221004, Jiangsu, China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou, 221004, Jiangsu, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China (mainland).
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China (mainland).|Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, 221004, Jiangsu, China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou, 221004, Jiangsu, China.
authors.forename: Han
authors.initials: H
authors.lastname: Shao
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China (mainland).
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China (mainland).|Department of Anesthesiology, General Hospital of Fuzhou Army Region, Fuzhou, 350025, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China (mainland).
authors.forename: Qian
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China (mainland).
authors.forename: Ying
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China (mainland).
authors.forename: Jinbao
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China (mainland).
authors.forename: Jinjun
authors.initials: J
authors.lastname: Bian
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China (mainland).
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology and Intensive Care, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China (mainland).
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Deng
mesh_terms: D000818:Animals; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D007107:Immune System / Q000187:drug effects* / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008697:Methane / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D008697:Methane