Organic Dust-Induced Lung Injury and Repair: Bi-Directional Regulation by TNFa and IL-10

Details

• Personal Author:
  Chandra D ; DeVasure JM ; Nelson AJ ; Nemecek M ; Poole JA ; Romberger DJ ; Wyatt TA
• Description:
  Exposure to organic dust increases chronic airway inflammatory disorders. Effective treatment strategies are lacking. It has been reported that hog barn dust extracts (HDE) induce TNFalpha through protein kinase C (PKC) activation and that lung inflammation is enhanced in scavenger receptor A (SRA/CD204) knockout (KO) mice following HDE. Because interleukin (IL)-10 production can limit excessive inflammation, it was hypothesized here that HDE-induced IL-10 would require CD204 to effect inflammatory responses. C57BL/6 wild-type (WT), SRA KO, and IL-10 KO mice were intranasally challenged daily for 8 days with HDE and subsequently rested for 3 days with/without recombinant IL-10 (rIL-10) treatment. Primary peritoneal macrophages (PM) and murine alveolar macrophages (MH-S cells) were treated in vitro with HDE, SRA ligand (fucoidan), rIL-10, and/or PKC isoform inhibitors. HDE induced in vivo lung IL-10 in WT, but not SRA KO mice, and similar trends were demonstrated in isolated PM from same treated mice. Lung lymphocyte aggregates and neutrophils were elevated in in vivo HDE-treated SRA and IL-10 KO mice after a 3-d recovery, and treatment during recovery with rIL-10 abrogated these responses. In vitro rIL-10 treatment reduced HDE-stimulated TNFalpha release in MH-S and WT PM. In SRA KO macrophages, there was reduced IL-10 and PKC zeta (z) activity and increased TNFalpha following in vitro HDE stimulation. Similarly, blocking SRA (24 hr fucoidan pre-treatment) resulted in enhanced HDE-stimulated macrophage TNFalpha and decreased IL-10 and PKCz activation. PKCz inhibitors blocked HDE-stimulated IL-10, but not TNFalpha. Collectively, HDE stimulates IL-10 by an SRA- and PKCz-dependent mechanism to regulate TNFalpha. Enhancing resolution of dust-mediated lung inflammation through targeting IL-10 and/or SRA may represent new approaches to therapeutic interventions. [Description provided by NIOSH]
• Subjects:
  Agriculture Animals Blood Dust Immune System Lung Diseases Macrophages Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Agricultural Industry Airway Resistance Alpha Animal Husbandry Workers Animal Studies Author Keywords: Hog Barn Dust CD204 IL-10 Immune Reaction Lung Lung Disease Macrophage Organic Dusts PKCz Respiratory Diseases Swine TNF

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• ISSN:
  1547-691X
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  153-162
• Volume:
  17
• Issue:
  1
• NIOSHTIC Number:
  nn:20061561
• Citation:
  J Immunotoxicol 2020 Dec; 17(1):153-162
• Contact Point Address:
  Todd A. Wyatt, 985910 Pulmonary, Critical Care, and Sleep, University of Nebraska Medical Center, Omaha, NE 68198-5910, USA
• Email:
  twyatt@unmc.edu
• Federal Fiscal Year:
  2021
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  Journal of Immunotoxicology
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ce789b5964e8fdf88a63df608ed655161e111ee3206df41afc273f302e4c7e1afe28a2c1951bb09537f838f267733f5db9d6262070fae0877caf185ef92af84e
• Download URL:
  https://stacks.cdc.gov/view/cdc/225065/cdc_225065_DS1.pdf
• File Type:
  [PDF - 1.37 MB ]