Veterinary Research Communications

, Volume 37, Issue 2, pp 145–154 | Cite as

Streptolysin-O/antibiotics adjunct therapy modulates site-specific expression of extracellular matrix and inflammatory genes in lungs of Rhodococcus equi infected foals

  • Volkan Gurel
  • Kristyn Lambert
  • Allen E. Page
  • Alan T. Loynachan
  • Katherine Huges
  • John F. Timoney
  • Michael Fettinger
  • David W. Horohov
  • John McMichael
Original Article

Abstract

The addition of streptolysin-O (SLO) to the standard antibiotics regimen was shown to be superior to antibiotics alone after experimental infection of foals with Rhodoccocus equi (R. equi). The objective of this study is to investigate this response by determining the site-specific expression of extracellular matrix (ECM) and inflammatory response genes in biopsy samples taken from three distinct lung regions of the infected foals. Twenty-four foals were challenged by intrabronchial instillation of R. equi and assigned to four treatment groups: SLO/antibiotics adjunct therapy, antibiotics-only therapy (7.5 mg/kg clarithromycin and 5 mg/kg rifampin), SLO-only, and saline-only treatments. Treatments were administered twice daily for 16 days unless symptoms progressed to the point where the foals needed to be euthanized. Gene expressions were determined using custom-designed equine real-time qPCR arrays containing forty-eight genes from ECM remodeling and inflammation pathways. A non-parametric Wilcoxon signed-rank test for independent samples was applied to two pairs of time-matched comparison groups, SLO/antibiotics vs. antibiotics-only and SLO-only vs. saline-only, to document the significant differences in gene expressions within these groups. Several genes, MMP9, MMP2, TIMP2, COL1A1, COL12A1, ITGAL, ITGB1, FN1, CCL2, CCL3, CXCL9, TNFα, SMAD7, CD40, IL10, TGFB1, and TLR2, were significantly regulated compared to the unchallenged/untreated control foals. The results of this study demonstrate that enhancement of clinical responses by SLO is consistent with the changes in expression of critical genes in ECM remodeling and inflammatory response pathways.

Keywords

Rhodococcus equi Streptolysin-O Adjunct therapy Gene expression Extracellular matrix Autoimmunity 

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Volkan Gurel
    • 1
  • Kristyn Lambert
    • 1
  • Allen E. Page
    • 2
  • Alan T. Loynachan
    • 3
  • Katherine Huges
    • 2
  • John F. Timoney
    • 2
  • Michael Fettinger
    • 2
  • David W. Horohov
    • 2
  • John McMichael
    • 1
  1. 1.Beech Tree Labs IncProvidenceUSA
  2. 2.Maxwell H. Gluck Equine Research Center, Department of Veterinary SciencesUniversity of KentuckyLexingtonUSA
  3. 3.University of Kentucky Veterinary Diagnostic LaboratoryLexingtonUSA

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