Human apolipoprotein E genotypes modify disease severity in experimental house dust mite-induced asthma

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NHLBI	IMMUNO/INFLAM-32

Authors

• X Yao
• C Dai
• KF Fredrikkson
• KJ Keeran
• GJ Zywicke
• X Qu
• Z Yu
• N Jefferies
• JP Lin
• M Kaler
• R Shamburek
• R Costello
• G Csako
• M Dahl
• BG Nordestgaard
• AT Remaley
• SJ Levine

Abstract

To assess whether human apolipoprotein E (apoE) alleles (ε2, ε3 and ε4) modify HDM-induced asthma. Asthma was induced by nasal HDM challenge in mice expressing the human apoE ε2 (huApoE2), ε3 (huApoE3) or ε4 (huApoE4) alleles and compared to mice expressing the endogenous murine apoE gene (muApoE). The huApoE3 mice displayed significant reductions in AHR, goblet cell hyperplasia and airway inflammation as compared to muApoE mice. The attenuated severity of airway inflammation in huApoE3 mice was mediated by reductions in lung mRNA levels of Th2 and Th17 cytokines, as well as chemokines (CCL7, CCL11, CCL24) and products of alternatively activated macrophages. The huApoE4 mice had an intermediate phenotype, with attenuated AHR and IgE production, as compared to muApoE mice, whereas airway inflammation and goblet cell hyperplasia were not reduced. In contrast, the manifestations of HDM-induced asthma were not modified in mice expressing the human apoE ε2 allele. Our study demonstrates that the polymorphic human apoE alleles differentially modulate the manifestations of experimental house dust mite-induced asthma, which can be stratified, in rank order of increasing disease severity, ε3 < ε4 < ε2. These results support the concept that polymorphic apoE alleles may modify disease severity in human asthma.

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