Prolyl endopeptidase inhibitors in neutrophilic lung inflammation in mice

M. Abdul Roda, G. Bezemer, F. Redegeld, A. Gaggar, E. Blalock, G. Folkerts

Research output: Contribution to conferenceAbstractOther research output

Abstract

RATIONALE In several lung diseases, including chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), collagen is broken down due to neutrophilia. The tripeptide Proline-Glicine-Proline (PGP) has been shown to be a pro-inflammatory metabolite of collagen due to its chemo attractive and activating properties towards neutrophils. Prolyl endopeptidase (PE) is involved in the enzymatic cascade to form PGP. Therefore, inhibiting PE might lead to less neutrophilic influx. METHODS ZPP, KYP-2047 and S-17092 are PE-specific inhibitors which were used in an in-vivo set-up in Balb/c mice (10-12 weeks old). The mice (n=3-6) were whole-body exposed to air-diluted cigarette smoke or air twice daily during 5 consecutive days and sacrificed on day 6. Thirty minutes prior to each exposure, the mice were treated with a PE inhibitor (125uM), dexamethasone (0.5mg/kg), PBS or solvent solution (0.25% DMSO). Bronchoalveolar lavage fluids (BALF) where collected to measure cell counts. Data were analyzed using a one-way ANOVA test with a post hoc Bonferroni test. RESULTS Mice treated with ZPP showed a significant decrease in total cell counts in BALF of 50.7% (P
Original languageEnglish
Publication statusPublished - 1 Jan 2013

Keywords

  • prolyl endopeptidase inhibitor
  • dexamethasone
  • proline
  • collagen
  • cigarette smoke
  • prolyl endopeptidase
  • tripeptide
  • solvent
  • dimethyl sulfoxide
  • pneumonia
  • mouse
  • American
  • society
  • neutrophil
  • cell count
  • metabolite
  • exposure
  • macrophage
  • neutrophil count
  • inflammation
  • chronic obstructive lung disease
  • neutrophilia
  • animal model
  • epithelium cell
  • smoke
  • Bagg albino mouse
  • cystic fibrosis
  • lung disease
  • antiinflammatory activity
  • cell differentiation
  • lung lavage
  • model
  • analysis of variance

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