Organic Dust Augments Nucleotide-Binding Oligomerization Domain Expression via an NF-kB Pathway to Negatively Regulate Inflammatory Responses

Details

• Personal Author:
  Gleason AM ; Kielian T ; Palm K ; Poole JA ; Romberger DJ ; Stone J ; West WW ; Wyatt TA
• Description:
  Nucleotide-binding oligomerization domain 2 (NOD2) is involved in innate immune responses to peptidoglycan degradation products. Peptidoglycans are important mediators of organic dust-induced airway diseases in exposed agriculture workers; however, the role of NOD2 in response to complex organic dust is unknown. Monocytes/macrophages were exposed to swine facility organic dust extract (ODE), whereupon NOD2 expression was evaluated by real-time PCR and Western blot. ODE induced significant NOD2 mRNA and protein expression at 24 and 48 h, respectively, which was mediated via a NF-KB signaling pathway as opposed to a TNF-a autocrine/paracrine mechanism. Specifically, NF-KB translocation increased rapidly following ODE stimulation as demonstrated by EMSA, and inhibition of the NF-KB pathway significantly reduced ODE-induced NOD2 expression. However, there was no significant reduction in ODE-induced NOD2 gene expression when TNF-a was inhibited or absent. Next, it was determined whether NOD2 regulated ODE-induced inflammatory cytokine production. Knockdown of NOD2 expression by small interfering RNA resulted in increased CXCL8 and IL-6, but not TNF-a production in response to ODE. Similarly, primary lung macrophages from NOD2 knockout mice demonstrated increased IL-6, CXCL1, and CXCL1, but not TNF-a, expression. Lastly, a higher degree of airway inflammation occurred in the absence of NOD2 following acute (single) and repetitive (3 wk) ODE exposure in an established in vivo murine model. In summary, ODE-induced NOD2 expression is directly dependent on NF-KB signaling, and NOD2 is a negative regulator of complex, organic dust-induced inflammatory cytokine/chemokine production in mononuclear phagocytes. [Description provided by NIOSH]
• Subjects:
  Animals Dust Immune System Livestock Lung Occupational Health Respiratory System Safety
• Keywords:
  Airway Animal Studies Author Keywords: Cytokines Cellular Effects Cellular Function Chemokines Cytokines Gram-positive Components Immune Reaction Inflammation Livestock Industry Lung Cells Monocyte/Macrophage Organic Dust Extract Organic Dusts Pathogen-associated Molecular Patterns Pattern Recognition Receptor Physiological Response Signaling Pathways SiRNA Swine/Hog/Pig

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• ISSN:
  1040-0605
• Document Type:
  Text
• Funding:
  Grant
• 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
• Volume:
  301
• Issue:
  3
• NIOSHTIC Number:
  nn:20053157
• Citation:
  Am J Physiol Lung Cell Mol Physiol 2011 Sep; 301(3):L296-L306
• Contact Point Address:
  J. A. Poole, Pulmonary, Critical Care, Sleep & Allergy Division; Dept. of Medicine, Univ. of Nebraska Medical Center, 985300 The Nebraska Medical Center, Omaha, NE 68198-5300
• Email:
  japoole@unmc.edu
• Federal Fiscal Year:
  2011
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center, Omaha, Nebraska
• Peer Reviewed:
  True
• Start Date:
  20060801
• Source Full Name:
  American Journal of Physiology: Lung Cellular and Molecular Physiology
• End Date:
  20160731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:3496ffe70a4d30b8bf75546e270c14480fc6c90c0c6529ccc74487688b06559381bd2a21454103e1fd12d626da0fe2de71c2722eb9448fa76a8d60e2a24ea7ba
• Download URL:
  https://stacks.cdc.gov/view/cdc/215971/cdc_215971_DS1.pdf
• File Type:
  [PDF - 1.02 MB ]