title: Protective effect of TM6 on LPS-induced acute lung injury in mice.
abstract: Acute lung injury (ALI) is an acute failure of the respiratory system for which effective treatment is urgently necessary. Previous studies found that several peptides potently inhibited the production of cytokines induced by lipopolysaccharide (LPS). In this study, we synthetized a cell-permeable TIR domain-derived decoy peptide (TM6) and examined its substance for the ability to inhibit TLR signaling in the model of ALI induced by LPS. We demonstrated that TM6 (2.5, 5 and 10 nmol/g) alleviated the histological changes in the lung tissues as well as myeloperoxtidase (MPO) activity, lung W/D ratio, the production of TNF-α, IL-1β and IL-6 induced by LPS. Furthermore, the numbers of total cells, neutrophils and macrophages in the BALF were suppressed by TM6. In vitro, TM6 (5, 10 and 20 µM) inhibited the production of TNF-α, IL-1β and IL-6 in LPS-stimulated alveolar macrophages. Moreover, the activation of Nuclear factor-kappaB (NF-κB) and Mitogen activated protein kinases (MAPK) signaling pathways induced by LPS were also inhibited by TM6. Collectively, our results suggested that TM6 was an effective inhibitor of ALI induced by LPS, and this peptide may very well serve as a future treatment for ALI.
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, 130062, P.R. China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, 130062, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, 130062, P.R. China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Qu
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, 130062, P.R. China.
authors.forename: Yongguo
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, 130062, P.R. China.
authors.forename: Shumin
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, 130062, P.R. China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, 130062, P.R. China.
authors.forename: Zecai
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, 130062, P.R. China. zhangns@jlu.edu.cn.
authors.forename: Naisheng
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, 130062, P.R. China. fuyunhesky@sina.com.
authors.forename: Yunhe
authors.initials: Y
authors.lastname: Fu
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000517:prevention & control; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*
chemical_list: D057846:Cell-Penetrating Peptides; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D020011:Protective Agents; D009195:Peroxidase; D020928:Mitogen-Activated Protein Kinases