E-GEOD-49047 - Overexpression of Dimethylarginine Dimethylaminohydrolase 1 Attenuates Airway Inflammation in Mouse Models of Asthma

Status
Released on 3 December 2013, last updated on 3 June 2014
Organism
Mus musculus
Samples (8)
Protocols (2)
Description
Levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, are increased in lung, sputum, exhaled breath condensate and plasma samples from asthma patients. ADMA is metabolized primarily by dimethylarginine dimethylaminohydrolase 1 (DDAH1) and DDAH2. We determined the effect of DDAH1 overexpression on development of allergic inflammation in mouse models of asthma. Wild type and DDAH1-transgenic mice were challenged with PBS or house dust mite (HDM). Airway inflammation was assessed by bronchoalveolar lavage (BAL) total and differential cell counts. Gene expression in lungs was determined by RNA-Seq and RT-quantitative PCR (qPCR). The expression of DDAH1 and DDAH2 was decreased in the lungs of mice following HDM exposure. Transgenic overexpression of DDAH1 resulted in decreased BAL total cell and eosinophil numbers following HDM exposure. Total IgE levels in serum and BAL fluid were decreased in HDM-exposed DDAH1-transgenic mice compared to HDM-exposed wild type mice. RNA-Seq results showed downregulation of genes in inducible nitric oxide synthase (iNOS) signaling pathway in PBS-treated DDAH1 transgenic mice versus PBS-treated wild type mice and downregulation of genes in IL-13/FOXA2 signaling pathway in HDM-treated DDAH1 transgenic mice versus HDM-treated wild type mice. Our findings suggest that decreased expression of DDAH1 in airway epithelial cells may contribute to allergic asthma and overexpression of DDAH1 attenuates allergen-induced airway inflammation through modulation of Th2 responses. mRNA profiles of WT and DDAH1-transgenic mice treated with PBS or house dust mite (HDM).
Experiment type
RNA-seq of coding RNA 
Contacts
Jing Chen <geo@ncbi.nlm.nih.gov>, Aaron M Gibson, Brandy Day, Gurjit K Khurana Hershey, Jingyuan Deng, Kayla G Kinker, Mario Medvedovic, Stacey A Bass, Weiguo Chen
MINSEQE
Exp. designProtocolsFactorsProcessedSeq. reads
Files
Investigation descriptionE-GEOD-49047.idf.txt
Sample and data relationshipE-GEOD-49047.sdrf.txt
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