An α4β1 integrin antagonist decreases airway inflammation in ovalbumin-exposed mice

Nicholas Kenyon, Ruiwu Liu, Erin M. O'Roark, Wenzhe Huang, Li Peng, Kit Lam

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Inhibition of the α4 subunit of both the α4β1 and α4β7 integrins has shown promise in decreasing airway inflammation and airway hyperresponsiveness in various animal models. We hypothesized that a novel, high-affinity α4β1 antagonist (LLP2A) would decrease the migration of eosinophils to the lung and ameliorate the airway hyperresponsiveness in a mouse model of ovalbumin-induced airway inflammation. To test this hypothesis, we administered LLP2A, or scrambled LLP2A (a negative control), prior to exposure of sensitized BALB/c mice to ovalbumin aerosol. We can partially prevent, or reverse, the airway inflammatory response, but not airways hyperresponsiveness, by treatment of mice with LLP2A, a synthetic peptidomimetic α4β1 antagonist. Specifically engineered, PEGylated (PEG) formulations of this antagonist further reduce the airway inflammatory response to ovalbumin, presumably by improving the circulating half-life of the drug.

Original languageEnglish (US)
Pages (from-to)138-146
Number of pages9
JournalEuropean Journal of Pharmacology
Volume603
Issue number1-3
DOIs
StatePublished - Jan 28 2009

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Keywords

  • α4β1 integrin
  • Airway hyperresponsiveness
  • Asthma
  • Eosinophil
  • PEGylated antagonist

ASJC Scopus subject areas

  • Pharmacology

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