title: Epigallocatechin-3-gallate alleviates paraquat-induced acute lung injury and inhibits upregulation of toll-like receptors.
abstract: OBJECTIVE
  To evaluate the detoxifying effect of epigallocatechin-3-gallate (EGCG) on paraquat (PQ)-induced acute lung injury in mice, and to explore the action mechanisms.
  
  
  METHODS
  Following administration of PQ, the mice received a low, a medium or a high dose of EGCG daily for three days. Histopathology of the lungs were examined by H&E staining. The levels of inflammatory cytokines, such as TNF-α, IL-1β and IL-6, in the bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay. Activation of NF-κB was assessed by Western blot and electrophoretic mobility gel shift assay. The expression of toll-like receptor (TLR)-2, 4, 9 and TLR adaptors (MyD88 and TRAF6) was detected by Western blot and immunohistochemical staining. The protective effect of EGCG against PQ toxicity was validated in vitro using A549 lung cancer cell line.
  
  
  RESULTS
  Treatment with EGCG dose-dependently attenuated PQ-induced acute lung injury in mice by reducing alveolar edema, hemorrhage, inflammatory cell infiltration and production of inflammatory cytokines. EGCG inhibited the activation of NF-κB and the upregulation of TLR 2, 4 and 9 as well as their adaptors MyD88 and TRAF6 in the lungs following PQ challenge. In addition, EGCG significantly reduced PQ-induced cell death, cytokine production, activation of NF-κB, and upregulation of TLRs and adaptors in A549 cells.
  
  
  CONCLUSIONS
  Our data suggest that TLR-mediated activation of NF-κB in the non-immune pulmonary cells could be involved in PQ-induced acute lung injury, and it may serve as a target of EGCG against PQ pulmonary toxicity.
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: Zhenning
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
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: D000072283:A549 Cells; D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D010269:Paraquat / Q000009:adverse effects*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D002392:Catechin; C045651:epigallocatechin gallate; D010269:Paraquat
keywords: Acute lung injury; Epigallocatechin-3-gallate; NF-κB; Paraquat; Toll-like receptor