We have identified that apolipoprotein E serves as an endogenous negative regulator of airway hyperreactivity and goblet cell hyperplasia in asthma by a low density lipoprotein receptor(LDLR)-dependent mechanism (Apolipoprotein E Negatively Regulates House Dust Mite-induced Asthma via a LDL Receptor-mediated Pathway. Yao X, Fredriksson K, Yu ZX, Xu X, Raghavachari N, Keeran KJ, Zywicke GJ, Kwak M, Amar MJ, Remaley AT, Levine SJ. Am J Respir Crit Care Med. 2010 Jul 9. Epub ahead of print). The effects of apoE, which is synthesized by macrophages in the lung, are mediated via binding to LDLRs that are expressed on ciliated airway epithelial cells. This project will utilize apolipoprotein receptor knock-out mice to define the role of other apolipoprotein receptors in modulating the pathogenesis of asthma. Furthermore, the mechanisms by which asthma pathogenesis is modulated by lung apolipoprotein receptors will be characterized.

Project Start
Project End
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Budget End
Support Year
4
Fiscal Year
2013
Total Cost
$328,659
Indirect Cost
Name
National Heart, Lung, and Blood Institute
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Type
DUNS #
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Fredriksson, Karin; Mishra, Amarjit; Lam, Jonathan K et al. (2014) The very low density lipoprotein receptor attenuates house dust mite-induced airway inflammation by suppressing dendritic cell-mediated adaptive immune responses. J Immunol 192:4497-509
Dai, Cuilian; Yao, Xianglan; Vaisman, Boris et al. (2014) The ABCA1 Transporter Attenuates Ovalbumin-induced Neutrophilic Airway Inflammation. Am J Respir Cell Mol Biol :