MyD88 Controls Airway Epithelial Muc5ac Expression During TLR Activation Conditions from Agricultural Organic Dust Exposure

Details

• Personal Author:
  Bailey KL ; Dickey BF ; Dickinson JD ; Jaramillo AM ; Nelson AJ ; Poole JA ; Staab EB ; Sweeter JM ; Warren KJ
• Description:
  Inflammation from airborne microbes can overwhelm compensatory mucociliary clearance mechanisms, leading to mucous cell metaplasia. Toll-like receptor (TLR) activation via myeloid differentiation factor 88 (MyD88) signaling is central to pathogen responses. We have previously shown that agricultural organic dust extract (ODE), with abundant microbial component diversity, activates TLR-induced airway inflammation. With the use of an established model, C57BL/6J wild-type (WT) and global MyD88 knockout (KO) mice were treated with intranasal inhalation of ODE or saline, daily for 1 wk. ODE primarily increased mucin (Muc)5ac levels relative to Muc5b. Compared with ODE-challenged WT mice, ODE-challenged, MyD88-deficient mice demonstrated significantly increased Muc5ac immunostaining, protein levels by immunoblot, and expression by quantitative PCR. The enhanced Muc5ac levels in MyD88-deficient mice were not explained by differences in the differentiation program of airway secretory cells in naïve mice. Increased Muc5ac levels in MyD88-deficient mice were also not explained by augmented inflammation, IL-17A, or neutrophil elastase levels. Furthermore, the enhanced airway mucins in the MyD88- deficient mice were not due to defective secretion, as the mucin secretory capacity of MyD88-KO mice remained intact. Finally, ODE-induced Muc5ac levels were enhanced in MyD88-deficient airway epithelial cells in vitro. In conclusion, MyD88 deficiency enhances airway mucous cell metaplasia under environments with high TLR activation. [Description provided by NIOSH]
• Subjects:
  Agriculture Antibodies Asthma Asthma, Occupational Dust Immune System Lung Microbiology Occupational Health Pathology Respiratory System Safety

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• Keywords:
  Airway Airway Obstruction Author Keywords: Agriculture Chronic Inflammation Dust Exposure Epithelial Glycoproteins Immune Reaction Lung Lung Cells Microorganisms Muc5ac Muc5b Mucin MyD88 Neutrophils Organic Dust Organic Dusts

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• ISSN:
  1040-0605
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 6 ; OSHA Region 7 ; Texas
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  316
• Issue:
  2
• NIOSHTIC Number:
  nn:20054839
• Citation:
  Am J Physiol Lung Cell Mol Physiol 2019 Feb; 316(2):L334-L347
• Contact Point Address:
  J. D. Dickinson, Pulmonary, Critical Care, Sleep & Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center, 985910 Nebraska Medical Center, Omaha, NE 68198-5910
• Email:
  jdickins@unmc.edu
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  American Journal of Physiology: Lung Cellular and Molecular Physiology
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:27e4dbd285fd6d517971ee7b5476afaa199eb107f3f7183dbfd64035492d8cc66cd85b846828ff8e9cec89d6fea59cc9372e3be02c7beec653a79ec0d8140dad
• Download URL:
  https://stacks.cdc.gov/view/cdc/217259/cdc_217259_DS1.pdf
• File Type:
  [PDF - 4.76 MB ]