title: Ethyl pyruvate decreases airway neutrophil infiltration partly through a high mobility group box 1-dependent mechanism in a chemical-induced murine asthma model.
abstract: BACKGROUND
  Diisocyanates are one of the leading causes of occupational asthma, which is dominated by granulocytic inflammation in the airway. In this study, we intended to explore the role of ethyl pyruvate (EP) on neutrophil infiltration in a toluene-2,4-diisocyanate (TDI)-induced murine asthma model.
  
  
  METHODS
  The experimental mice were first dermally sensitized and then challenged with TDI via oropharyngeal aspiration. The mice were treated intraperitoneally with 100, 50 or 10mg/kg EP 1h before each challenge. One day after the last challenge, airway reactivity to methacholine was measured by a barometric plethysmographic chamber. Total and differential cell counts, along with levels of macrophage inflammatory protein-2 (MIP-2), TNF-α in bronchoalveolar lavage (BAL) fluid and mRNA expression of CXCR2 in the lung were assessed. To depict neutrophils, a naphthol AS-D chloroacetate esterase kit was used. High mobility group box 1 (HMGB1) was determined by western blot and immunohistochemistry.
  
  
  RESULTS
  Treatment with EP dramatically decreased airway hyperresponsiveness in TDI-challenged mice, as well as numbers of neutrophils in BAL fluid and peribronchovascular regions. Both the TDI-induced raised protein level and abnormal distribution of HMGB1 were significantly recovered by EP in a dose-dependent manner. The concentration of MIP-2 in TDI-induced asthma mice was significantly higher than that of the control ones, while EP had few effects on MIP-2. The mRNA expression of CXCR2 didn't change significantly, and TNF-α was not detected in BAL fluids.
  
  
  CONCLUSIONS
  EP reduces airway neutrophil infiltration partly through downregulating HMGB1 in a chemical-induced murine asthma model.
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Haixiong
authors.initials: H
authors.lastname: Tang
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Haijin
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Jiafu
authors.initials: J
authors.lastname: Song
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Hangming
authors.initials: H
authors.lastname: Dong
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Yao
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: LV
authors.affiliation: School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
authors.affiliation: Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address: caishaox@fimmu.com.
authors.forename: Shaoxi
authors.initials: S
authors.lastname: Cai
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D054426:Chemokine CXCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D011773:Pyruvates / Q000008:administration & dosage*; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism; D014051:Toluene 2,4-Diisocyanate / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; D024243:HMGB1 Protein; D011773:Pyruvates; D023063:Receptors, Interleukin-8B; D014409:Tumor Necrosis Factor-alpha; C046522:ethyl pyruvate; D014051:Toluene 2,4-Diisocyanate
keywords: Asthma; Ethyl pyruvate; Neutrophil; Toluene-2,4-diisocyanate