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2621422 
Journal Article 
Abstract 
An apolipoprotein E mimetic peptide inhibits airway hyperreactivity in a house dust mite model of allergic asthma 
Yao, X; Fredriksson, K; Amar, M; Remaley, AT; Levine, SJ 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A2836 
English 
WOS:000208771001748 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Severe asthma is associated with the persistent expression of key disease severity genes despite treatment with corticosteroids. We used genome-wide expression profiling of the lung transcriptome to identify the up-regulated expression of apolipoprotein E (apoE) in a house dust mite (HDM) model of murine asthma following corticosteroid treatment. We also found that HDM-challenged apoE-/- mice have increased airway hyperreactivity (AHR) and mucin gene expression as compared to wild-type mice, whereas indices of airway inflammation were not affected. Here, we assessed whether reconstitution of the apoE deficiency in HDM-challenged apoE-/- mice with an apoE mimetic peptide can rescue the phenotype of enhanced AHR and goblet cell hyperplasia. An apoE(130 – 149) mimetic peptide, corresponding to the apoE receptor binding domain, or a control scrambled peptide, were administered to apoE-/- mice via an osmotic mini-pump prior to the induction of allergic asthma by daily nasal HDM challenge for 5 days per week for 5 weeks. The apoE(130-149) mimetic peptide completely inhibited the induction of AHR and goblet cell hyperplasia, while mRNAs encoding MUC5AC and CLCA3 were significantly reduced. Administration of the apoE(130-149) mimetic peptide also significantly inhibited the induction of allergen-mediated airway inflammation and IgE production. We next assessed whether the apoE(130-149) mimetic peptide could be effective for the treatment of established asthma. Wild-type A/J mice that received nasal HDM for 5 days/week for 6 weeks were treated with the apoE(130-149) mimetic peptide during weeks 4 to 6. Treatment with the apoE(130-149) mimetic peptide reduced AHR to levels similar to that of control mice. Similarly, administration of the apoE(130-149) mimetic peptide significantly reduced mRNA levels of MUC5AC, CLCA3, IL-13 and IL-17A, but did not inhibit airway inflammation. These results demonstrate that administration of an apoE mimetic peptide rescues the phenotype of asthmatic apoE-/- mice and inhibits the induction of asthma. Furthermore, treatment with the apoE(130-149) mimetic peptide completely reversed AHR and attenuated mucin gene expression in established asthma. Taken together, these findings support the concept of developing apoE-based strategies as a new approach for the treatment of asthma. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010