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

D. Schneberger, J. R. Gordon, J. M. DeVasure, J. A. Boten, A. J. Heires, Debra Romberger, Todd A Wyatt

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 PKCα and PKCε 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.

Original languageEnglish (US)
Pages (from-to)55-62
Number of pages8
JournalPulmonary Pharmacology and Therapeutics
Volume31
DOIs
StatePublished - Apr 1 2015

Fingerprint

Dust
Pneumonia
Swine
Chemokines
Lung
Interleukin-8
Protein Kinase C
Neutrophils
Cytokines
Intercellular Adhesion Molecule-1
Nose
Innate Immunity
Endotoxins
Inhalation
Interleukin-6
Animals
Chemical activation
Injections

Keywords

  • Chemokines
  • Cytokines
  • G31P
  • IL-8
  • Occupational dusts

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Biochemistry, medical
  • Pharmacology (medical)

Cite this

CXCR1/CXCR2 antagonist CXCL8(3-74)K11R/G31P blocks lung inflammation in swine barn dust-instilled mice. / Schneberger, D.; Gordon, J. R.; DeVasure, J. M.; Boten, J. A.; Heires, A. J.; Romberger, Debra; Wyatt, Todd A.

In: Pulmonary Pharmacology and Therapeutics, Vol. 31, 01.04.2015, p. 55-62.

Research output: Contribution to journalArticle

Schneberger, D. ; Gordon, J. R. ; DeVasure, J. M. ; Boten, J. A. ; Heires, A. J. ; Romberger, Debra ; Wyatt, Todd A. / CXCR1/CXCR2 antagonist CXCL8(3-74)K11R/G31P blocks lung inflammation in swine barn dust-instilled mice. In: Pulmonary Pharmacology and Therapeutics. 2015 ; Vol. 31. pp. 55-62.
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AB - 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 PKCα and PKCε 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.

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