CXCR1/CXCR2 antagonist CXCL8(3-74)K11R/G31P blocks lung inflammation in swine barn dust-instilled mice

Details

• Personal Author:
  Boten JA ; DeVasure JM ; Gordon JR ; Heires AJ ; Romberger DJ ; Schneberger D ; Wyatt TA
• Description:
  Inhalation of agricultural occupational dusts from swine confinement facilities can result in lung inflammation. The innate immune response to organic barn dusts results in production of a number of pro-inflammatory factors in the lungs of barn workers such as cytokines, chemokines, and an influx of neutrophils. Many of these inflammatory factors are influenced by the chemokine CXCL8/IL-8 (KC or MIP-2 in mice). Previously, we have demonstrated that an endotoxin-independent component of swine barn dust extract (SBE) elevates lung chemokines in a protein kinase C (PKC)-dependent manner resulting in the significant formation of lung inflammatory cell infiltrates in a mouse model of SBE injury. In this study we test the ability of a CXCR1/CXCR2 antagonist, CXCL8(3-74)K11R/G31P (G31P) to block many of the features of lung-inflammation in response to challenge with SBE in an established mouse exposure system. Injection of G31P concurrent with SBE nasal instillation over a course of 3 weeks significantly reduced neutrophil accumulation in the lungs of barn dust exposed animals compared to those given SBE alone. There was a similar reduction in pro-inflammatory cytokines and chemokines IL-6, KC, and MIP-2 in SBE plus G31P-treated mice. In addition to excreted products, the receptors ICAM-1, CXCR1, and CXCR2, which all were elevated with SBE exposure, were also decreased with G31P treatment. SBE activation of PKCa and PKCe was reduced as well with G31P treatment. Thus, G31P was found to be highly effective at reducing several features of lung inflammation in mice exposed to barn dust extracts. [Description provided by NIOSH]
• Subjects:
  Agriculture Animal Husbandry Animals Chronic Disease Dust Immune System Laboratories Lung Diseases Occupational Health Pathology Respiratory System Safety

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• Keywords:
  Agricultural-workers Animal-husbandry-workers Author Keywords: Occupational Dusts Chemokines Chronic-inflammation Cytokines Dust-exposure G31P IL-8 Immune-reaction Inhalation-studies Laboratory-animals Lung-disorders Organic-dusts

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• ISSN:
  1094-5539
• Document Type:
  Text
• Funding:
  Grant ; 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:
  55-62
• Volume:
  31
• NIOSHTIC Number:
  nn:20047340
• Citation:
  Pulm Pharmacol Ther 2015 Apr; 31:55-62
• Contact Point Address:
  Todd A. Wyatt, Pulmonary, Critical Care, Sleep & Allergy Division of the Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
• Email:
  twyatt@unmc.edu
• Federal Fiscal Year:
  2015
• 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:
  Pulmonary Pharmacology & Therateutics
• End Date:
  20160731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:260651ba90d3688c6f19b57c5c4b3feda14b31b0540c4b61c315f085d2f360a7f2a4851c25b3e7f08bbdd0885741264b5ebc8fc31ba6adf64cf1cb7f3ec9398f
• Download URL:
  https://stacks.cdc.gov/view/cdc/202445/cdc_202445_DS1.pdf
• File Type:
  [PDF - 3.48 MB ]