Activating transcription factor 3 protects mice against pseudomonas aeruginosa-induced acute lung injury by interacting with lipopolysaccharide binding protein. (October 2017)

• Record Type: Journal Article
• Authors: Zhao, Yunfeng; Wu, Xiulin; Qian, Lanlan; Guo, Liang; Liao, Jiangrong; Wu, Xueling
• Is Part Of: Molecular immunology. Volume 90(2017:Oct.)
• Page Start: 27
• Page End: 32
• Publication Date: 2017-10
• Subjects: ALI acute lung injury -- ATF3 activating transcription factor 3 -- PA pseudomonas aeruginosa -- KO knockout mice -- WT wild type -- BALF bronchoalveolar lavage fluid -- IL interleukin -- TNF αtumor necrosis factor α -- NFκa nuclear factor kappa B -- Co-ip Co-immunoprecipitation -- TLR4 toll-like receptor 4 -- LPS lipopolysaccharide -- LBP lipopolysaccharide binding protein -- ROS reactive oxygen species -- HDL high density lipoprotein -- qRT-PCR quantitative real time PCR -- ELISA enzyme linked immunosorbent assay -- μL microliter; Activating transcription factor 3 -- Acute lung injury -- Pseudomonas aeruginosa -- LPS-binding protein; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2017.06.037
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: ATF3 have a protective effect in ALI mice induced by PA. ATF3 weakened the activity of NF-κB through binding to LBP which inhibited the inflammation. The mechanism for ATF3 in inflammation is proposed. Abstract: Excessive inflammatory response is critical event in the pathogenesis of acute lung injury (ALI). Previous study has shown that activating transcription factor 3 (ATF3) plays a role in downregulate inflammatory responses including ventilation-induced ALI. We hypothesized that ATF3 have a protective effect in ALI induced by pseudomonas aeruginosa. PA was intra-tracheally administrated to ATF3 knock-out (KO) mice to establish ALI model. Inflammatory factors, BALF protein, lung wet to dry ratio, lung injury score and mortality were determined. The activation of NF-κB was detected by western blot and Co-immunoprecipitation (Co-ip) was used to determinate the binding of ATF3 to LBP. Peritoneal macrophages were isolated from ATF3 KO mice and stimulated by PA. PA increased the expression of ATF3 in the lung tissues in ATF3 wild type (WT) mice. ATF3 deficiency significantly increased the concentration of TNFα, IL-6 and IL-1β in the supernatant of peritoneal macrophages, lung tissue and BALF after PA stimulation and also enhanced the activity of NF-κB. ATF3 deficiency also enhanced the BALF protein concentration and increased the lung wet to dry ratio. The lung injury score and mortality were higher in ATF3 KO mice treated with PA. Moreover, ATF3 was demonstrated to bind to LBP These finding suggest ATF3 protect mice against ALI induced by PA partly due to the binding to LBP.