title: Toll-like receptor 9 mediates paraquat-induced acute lung injury: an in vitro and in vivo study.
abstract: OBJECTIVE
  This study aimed to investigate the role of Toll-like receptor 9 in paraquat-induced acute lung injury (ALI).
  
  
  METHODS
  For in vivo study,C57BL mice were randomly assigned into the vehicle control group, paraquat group, paraquat + TLR9 antagonist (ODN2088) group, and TLR9 antagonist (ODN2088) group (n=36 per group). After paraquat 30mg/kg ip for 2, 24 and 48h, serum samples and lung tissues were collected to evaluate ALI and TLR9 signaling by lung injury score, protein levels of TLR9, MyD88, p-IRAK4, p-p65, and serum TNF-α and IL-1β levels. As for in vitro research A549 cells were randomly divided into the control group, paraquat group, paraquat + TLR9 siRNA group, and TLR9 siRNA group. After paraquat treatment for 24h, the cells and supernatant were collected to measureTLR9, TNF-α, IL-1 mRNA expression, and detect activation of NF-κB, caspase-3.
  
  
  RESULTS
  In vivo, the lung injury score, the TLR9, MyD88, p-IRAK4 and p-p65 protein levels, and cytokines TNF-α and IL-1β levels in paraquat group were significantly higher than that in the control group;TLR9 blocker ODN2088 pretreatment attenuated lung injury, inhibited MyD88 and NF-κB activation, and reduced TNF-α and IL-1β in serum. In vitro result shows that the gene silencing of TLR9 reduced the mRNA expression of TLR9, TNF-α and IL-1, inhibited NF-κB and caspase-3 activation, attenuated cell apoptosis.
  
  
  CONCLUSIONS
  TLR9 mediates paraquat-induced ALI, antagonizing TLR9 or silencing TLR9gene may attenuate paraquat-induced ALI.
authors.affiliation: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Lichun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China. Electronic address: zhaom@sj-hospital.org.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D020868:Gene Silencing; D006540:Herbicides / Q000633:toxicity*; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D010269:Paraquat / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage; D013997:Time Factors; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D016207:Cytokines; D006540:Herbicides; D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3; D010269:Paraquat
keywords: Acute lung injury; Paraquat; Toll-like receptor 9