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2621424 
Journal Article 
Abstract 
The apolipoprotein A-I mimetic peptide, 5A, inhibits the induction of house dust mite-induced 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 
A5395 
English 
WOS:000208771003472 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
New treatment approaches are needed for patients with severe, corticosteroid-refractory asthma. Apolipoprotein A-I (apo A-I), a major constituent of high density lipoproteins, can prevent and reverse atherosclerosis by enhancing reverse cholesterol transport. ApoA-I has anti-inflammatory effects in atherosclerosis and also prevents dendritic cell maturation, lymphocyte activation, macrophage cytokine production, and neutrophil functions. This suggests that the anti-inflammatory effects of apolipoprotein A-I might be utilized in a therapeutic fashion to attenuate airway inflammation in asthma. Here, we assessed whether an apolipoprotein A-I mimetic peptide can inhibit the induction of allergic asthma. We utilized the 5A apoA-I mimetic peptide, which is a bihelical amphipathic peptide that mediates cholesterol efflux by the ABCA1 transporter. The 5A peptide was administered by osmotic mini-pump concurrent with the induction of allergic asthma by daily nasal house dust mite (HDM) challenge for 5 days per week for 5 weeks. Administration of the 5A peptide significantly reduced the total number of inflammatory cells recovered in bronchoalveolar lavage fluid (BALF), as well as the number of BALF eosinophils, lymphocytes and neutrophils. Histopathologic examination of lung sections confirmed that the 5A peptide attenuated airway inflammation in HDM-challenged mice. The 5A peptide significantly reduced lung mRNA levels of Th2 (IL-4 and IL-13) and Th17 (IL17A) cytokines, as well as lung mRNA levels of genes associated with goblet cell hyperplasia (MUC5AC and CLCA3). Lung mRNA levels of chitinase 3-like 3, arginase 1, and inducible nitric oxide synthase were also significantly reduced. Administration of the 5A peptide also completely inhibited the induction of airway hyperreactivity. Thus, we have shown that administration of the apolipoprotein A-I mimetic peptide, 5A, inhibits the induction of airway inflammation, mucin gene expression, and airway hyperreactivity in a HDM model of allergic asthma. These findings demonstrate that the 5A apoA-I mimetic peptide might be utilized as a novel therapeutic approach for patients with allergic asthma. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010