title: Knockdown of Burton's tyrosine kinase confers potent protection against sepsis-induced acute lung injury.
abstract: Sepsis is a common and critical complication in surgical patients that often leads to multiple organ failure syndrome (MOFS), including acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Despite intensive supportive care and treatment modalities, the mortality of these patients remains high. In this study, we investigated the role of Burton's tyrosine kinase (BTK), a member of the Btk/Tec family of cytoplasmic tyrosine kinases, in the pathogenesis of sepsis, and evaluated the protective effect of in vivo Btk RNA interference in a mouse model of cecal ligation and puncture (CLP)-induced sepsis. After intratracheal injection of Btk siRNA, the mice were then subjected to CLP to induce sepsis. The results demonstrated that this approach conferred potent protection against sepsis-induced ALI, as evidenced by a significant reduction in pathological scores, epithelial cell apoptosis, pulmonary edema, vascular permeability, and the expression of inflammatory cytokines and neutrophil infiltration in the lung tissues of septic mice. In addition, RNA interference of Btk significantly suppressed p-38 and iNOS signaling pathways in transduced alveolar macrophages in vitro. These results identify a novel role for BTK in lethal sepsis and provide a potential new therapeutic approach to sepsis and ALI.
authors.affiliation: Burn Institute of Chinese People's Liberation Army and Department of Burn Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Panyu
authors.initials: P
authors.lastname: Zhou
authors.forename: Bing
authors.initials: B
authors.lastname: Ma
authors.forename: Shuogui
authors.initials: S
authors.lastname: Xu
authors.forename: Shijie
authors.initials: S
authors.lastname: Zhang
authors.forename: Hongtai
authors.initials: H
authors.lastname: Tang
authors.forename: Shihui
authors.initials: S
authors.lastname: Zhu
authors.forename: Shichu
authors.initials: S
authors.lastname: Xiao
authors.forename: Daofeng
authors.initials: D
authors.lastname: Ben
authors.forename: Zhaofan
authors.initials: Z
authors.lastname: Xia
mesh_terms: D055371:Acute Lung Injury / Q000201:enzymology / Q000209:etiology* / Q000235:genetics*; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D055785:Gene Knockdown Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D012128:Respiratory Distress Syndrome / Q000201:enzymology / Q000209:etiology / Q000235:genetics; D018805:Sepsis / Q000150:complications*; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D034741:RNA, Small Interfering; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; D048051:p38 Mitogen-Activated Protein Kinases