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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) <jats:italic>ip<\/jats:italic> treatment (16\u2009ml\/kg) alleviated endotoxin shock, bacteria-induced sepsis and dextran-sulfate-sodium-induced colitis in mice via decreased production of TNF-\u03b1 and IL-6. In MS-treated macrophages, LPS-induced activation of NF-\u03bab\/MAPKs was attenuated. Interestingly, MS treatment significantly elevated the levels of IL-10 both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Neutralization of IL-10 abrogated the therapeutic effect of MS. Moreover, anti-IL10 blockade partially restored the MS-mediated attenuation of NF-\u03bab\/MAPKs phosphorylation. We further found that MS resulted in markedly enhanced phosphorylation of GSK-3\u03b2 and AKT, which both mediate the release of Il-10. Additionally, inhibition of PI3K attenuated MS-mediated p-GSK-3\u03b2 and IL-10 production and reversed the suppressed activation of NF-\u03bab\/ 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.<\/jats:p>","DOI":"10.1038\/srep29359","type":"journal-article","created":{"date-parts":[[2016,7,13]],"date-time":"2016-07-13T07:02:34Z","timestamp":1468393354000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Methane limit LPS-induced NF-\u03baB\/MAPKs signal in macrophages and suppress immune response in mice by enhancing PI3K\/AKT\/GSK-3\u03b2-mediated IL-10 expression"],"prefix":"10.1038","volume":"6","author":[{"given":"Xu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinbao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjun","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,7,11]]},"reference":[{"key":"BFsrep29359_CR1","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1126\/science.282.5396.2085","volume":"282","author":"A Poltorak","year":"1998","unstructured":"Poltorak, A. et al. 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