Ethyl Pyruvate Reduces Organic Dust-Induced Airway Inflammation by Targeting HMGB1-RAGE Signaling

Details

• Personal Author:
  Bhat SM ; Charavaryamath C ; Karriker LA ; Massey N ; Singh B
• Description:
  Background: Animal production workers are persistently exposed to organic dust and can suffer from a variety of respiratory disease symptoms and annual decline in lung function. The role of high mobility group box-1 (HMGB1) in inflammatory airway diseases is emerging. Hence, we tested a hypothesis that organic dust exposure of airway epithelial cells induces nucleocytoplasmic translocation of HMGB1 and blocking this translocation dampens organic dust-induced lung inflammation. Methods: Rats were exposed to either ambient air or swine barn (8 h/day for either 1, 5, or 20 days) and lung tissues were processed for immunohistochemistry. Swine barn dust was collected and organic dust extract (ODE) was prepared and sterilized. Human airway epithelial cell line (BEAS-2B) was exposed to either media or organic dust extract followed by treatment with media or ethyl pyruvate (EP) or anti-HMGB1 antibody. Immunoblotting, ELISA and other assays were performed at 0 (control), 6, 24 and 48 h. Data (as mean +/- SEM) was analyzed using one or two-way ANOVA followed by Bonferroni's post hoc comparison test. A p value of less than 0.05 was considered significant. Results: Compared to controls, barn exposed rats showed an increase in the expression of HMGB1 in the lungs. Compared to controls, ODE exposed BEAS-2B cells showed nucleocytoplasmic translocation of HMGB1, co-localization of HMGB1 and RAGE, reactive species and pro-inflammatory cytokine production. EP treatment reduced the ODE induced nucleocytoplasmic translocation of HMGB1, HMGB1 expression in the cytoplasmic fraction, GM-CSF and IL-1β production and augmented the production of TGF-B1 and IL-10. Anti-HMGB1 treatment reduced ODE-induced NF-kB p65 expression, IL-6, ROS and RNS but augmented TGF-B1 and IL-10 levels. Conclusions: HMGB1-RAGE signaling is an attractive target to abrogate OD-induced lung inflammation. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Animals Dust Lung Occupational Health Respiratory System Safety
• Keywords:
  Airborne Dusts Animal Husbandry Workers Animal Studies Author Keywords: Organic Dust Cell Signaling Cytokines Ethyl Pyruvate HMGB1 Lung Inflammation Lung Irritants Organic Dusts RAGE

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• ISSN:
  1465-9921
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Iowa ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  27
• Volume:
  20
• NIOSHTIC Number:
  nn:20054633
• Citation:
  Respir Res 2019 Feb; 20:27
• Contact Point Address:
  Chandrashekhar Charavaryamath, Department of Biomedical Sciences, 2008 Vet Med Building, Iowa State University, Ames, IA, USA
• Email:
  chandru@iastate.edu
• CAS Registry Number:
  Ethyl pyruvate (CAS RN 617-35-6)
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Iowa, Iowa City
• Peer Reviewed:
  True
• Start Date:
  20010930
• Source Full Name:
  Respiratory Research
• End Date:
  20270929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:cb07054b68f8e9c60722db40f984118c9aa156acc01e99ecfc011a485666161fd96ea56d9c4556b19012978e1ac147c1bf0616e313eb367056f9733556fc8189
• Download URL:
  https://stacks.cdc.gov/view/cdc/217115/cdc_217115_DS1.pdf
• File Type:
  [PDF - 6.13 MB ]