title: Rapamycin attenuates acute lung injury induced by LPS through inhibition of Th17 cell proliferation in mice.
abstract: Th17 cells have been confirmed to increase neutrophils through cytokine secretions. ALI/ARDS are characterized as neutrophil infiltration in inflammation cases; however, there is conflicting information concerning the role of Th17 cells in ALI/ARDS, as well as their potential treatment value. We measured Th17-linear cytokines in the plasma of patients with sepsis-related ARDS. The consistently high levels of IL-17 and IL-22 in the nonsurvivors suggested that overreaction of the Th17-mediated immune response may be a risk factor for poor outcomes. Th17 linear cytokines were also increased in an LPS-induced murine model of acute lung injury, along with neutrophil accumulation. The mice that completely lacked IL-17 failed to accumulate and activate neutrophils. Lung inflammation was obviously attenuated in the IL-17(-)/(-) mice. Meanwhile, the neutrophil count was markedly increased in the healthy WT mice challenged with recombinant IL-22 and IL-17. Rapamycin attenuated lung injury by inhibiting the differentiation of Th17 cells through RORγt and STAT3 dysfunction. Furthermore, we demonstrated that SOCS3 and Gfi1, which were responsible for the molecular suppression of RORγt and STAT3, were up-regulated by rapamycin. These results point toward a pivotal view to treatment of ALI through weakening the proliferation of Th17 cells with rapamycin.
authors.affiliation: Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Xiaoyu
authors.affiliation: Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing 400010, China.
authors.forename: Song
authors.initials: S
authors.lastname: Zhixin
authors.affiliation: Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Di
authors.affiliation: Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China.
authors.forename: Deng
authors.initials: D
authors.lastname: Xinyu
authors.affiliation: Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Jing
authors.affiliation: Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China.
authors.forename: He
authors.initials: H
authors.lastname: Jing
authors.affiliation: Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China.
authors.forename: Deng
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Xi
authors.affiliation: Department of Emergency Medicine, the Yongchuan Affiliated Hospital of Chongqing Medical University, 439 Xuanhua Road, Yongchuan District, Chongqing 402160, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Chunrong
authors.affiliation: Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong District, Chongqing 400010, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Daoxin
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology; D020123:Sirolimus / Q000494:pharmacology*; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000235:genetics / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology; D000097043:Interleukin-22
chemical_list: D004268:DNA-Binding Proteins; D020381:Interleukin-17; D007378:Interleukins; D008070:Lipopolysaccharides; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D050796:STAT3 Transcription Factor; D020123:Sirolimus; D000071223:Suppressor of Cytokine Signaling 3 Protein; D014157:Transcription Factors; D000097043:Interleukin-22; C079873:Gfi1 protein, mouse; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse