Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL006055-03
Application #
8558004
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2012
Total Cost
$303,853
Indirect Cost

  Institution

Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Mishra, Amarjit; Yao, Xianglan; Saxena, Ankit et al. (2018) Low-density lipoprotein receptor-related protein 1 attenuates house dust mite-induced eosinophilic airway inflammation by suppressing dendritic cell-mediated adaptive immune responses. J Allergy Clin Immunol 142:1066-1079.e6
Yao, Xianglan; Gordon, Elizabeth M; Barochia, Amisha V et al. (2016) The A's Have It: Developing Apolipoprotein A-I Mimetic Peptides Into a Novel Treatment for Asthma. Chest 150:283-8
Gordon, Elizabeth M; Figueroa, Debbie M; Barochia, Amisha V et al. (2016) High-density Lipoproteins and Apolipoprotein A-I: Potential New Players in the Prevention and Treatment of Lung Disease. Front Pharmacol 7:323
Yao, Xianglan; Gordon, Elizabeth M; Figueroa, Debbie M et al. (2016) Emerging Roles of Apolipoprotein E and Apolipoprotein A-I in the Pathogenesis and Treatment of Lung Disease. Am J Respir Cell Mol Biol 55:159-69
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) ATP-binding cassette transporter 1 attenuates ovalbumin-induced neutrophilic airway inflammation. Am J Respir Cell Mol Biol 51:626-36
Mishra, Amarjit; Yao, Xianglan; Levine, Stewart J (2013) From bedside to bench to clinic trials: identifying new treatments for severe asthma. Dis Model Mech 6:877-88
Yao, Xianglan; Fredriksson, Karin; Yu, Zu-Xi et al. (2010) Apolipoprotein E Negatively Regulates House Dust Mite-induced Asthma via a LDL Receptor-mediated Pathway. Am J Respir Crit Care Med :