title: MyD88 gene knockout attenuates paraquat-induced acute lung injury.
abstract: OBJECTIVE
  This study investigated the role of myeloid differentiation factor 88 (MyD88) in paraquat-induced acute lung injury (ALI).
  
  
  METHODS
  C57BL mice were divided into the control group, paraquat group, MyD88 knockout (KO) group, and MyD88 KO plus paraquat group. At 48h after paraquat poisoning, serum and lung tissues were collected. ELISA was employed to detect tumor necrosis factor-α (TNF-α) and interleukine-1β (IL-1β) contents in serum. Lung tissues were processed for hematoxylin-eosin staining, followed by histological scoring. PCR was performed to detect the mRNA expression of MyD88, TNF-α, and IL-1β in the lungs. Immunofluorescence staining was done to evaluate the expression and distribution of MyD88 and nuclear factor κB (NF-κB) in the lungs. Western blotting was conducted to detect the protein level of toll-like receptor (TLR) 4, TLR9, MyD88, and NF-κB in the lungs.
  
  
  RESULTS
  Paraquat poisoning significantly increased serum inflammatory cytokines, as well as MyD88, TLR4, TLR9, and NF-κB, and resulted in ALI. After MyD88 KO, the levels of inflammatory cytokines and NF-κB decreased markedly, and ALI was also attenuated although TLR4 and TLR9 expression continued at an elevated level.
  
  
  CONCLUSIONS
  MyD88 mediates paraquat-induced ALI, and MyD88 gene knockout may attenuate paraquat-induced ALI and reduce the production of proinflammatory cytokines.
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: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Lianghong
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Jia
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 / Q000235:genetics*; D000818:Animals; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010269:Paraquat / Q000506:poisoning*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics
chemical_list: D053583:Interleukin-1beta; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D010269:Paraquat
keywords: Acute lung injury; MyD88; Paraquat; Proinflammatory cytokines