title: Altered expression of microRNA in the airway wall in chronic asthma: miR-126 as a potential therapeutic target.
abstract: BACKGROUND
  The role of microRNAs (miRNAs) in regulating gene expression is currently an area of intense interest. Relatively little is known, however, about the role of miRNAs in inflammatory and immunologically-driven disorders. In a mouse model, we have previously shown that miRNAs are potentially important therapeutic targets in allergic asthma, because inhibition of miR-126, one of a small subset of miRNAs upregulated in the airway wall, effectively suppressed Th2-driven airway inflammation and other features of asthma. In the present study, we extended investigation of the therapeutic potential of miRNA inhibition to our well-established model of chronic asthma.
  
  
  METHODS
  Female BALB/c mice were systemically sensitised with ovalbumin (OVA) and chronically challenged with low mass concentrations of aerosolised OVA for up to 6 weeks. Airway tissue was obtained by blunt dissection and RNA was isolated for miRNA profiling. On the basis of the results obtained, animals were subsequently treated with either an antagomir to miR-126 (ant-miR-126) or a scrambled control antagomir once weekly during the 6 weeks of chronic challenge, and the effects on airway inflammation and remodelling were assessed using established morphometric techniques.
  
  
  RESULTS
  Compared to naïve mice, there was selective upregulation of a modest number of miRNAs, notably miR-126, in the airway wall tissue of chronically challenged animals. The relative increase was maximal after 2 weeks of inhalational challenge and subsequently declined to baseline levels. Compared to treatment with the scrambled control, ant-miR-126 significantly reduced recruitment of intraepithelial eosinophils, but had no effect on the chronic inflammatory response, or on changes of airway remodelling.
  
  
  CONCLUSIONS
  In this model of chronic asthma, there was an initial increase in expression of a small number of miRNAs in the airway wall, notably miR-126. However, this later declined to baseline levels, suggesting that sustained changes in miRNA may not be essential for perpetuation of chronic asthma. Moreover, inhibition of miR-126 by administration of an antagomir suppressed eosinophil recruitment into the airways but had no effect on chronic inflammation in the airway wall, or on changes of remodelling, suggesting that multiple miRNAs are likely to regulate the development of these lesions.
authors: Inflammation and Infection Research Centre, University of New South Wales, Sydney, Australia.
authors: Adam
authors: A
authors: Collison
authors: Cristan
authors: C
authors: Herbert
authors: Jessica S
authors: JS
authors: Siegle
authors: Joerg
authors: J
authors: Mattes
authors: Paul S
authors: PS
authors: Foster
authors: Rakesh K
authors: RK
authors: Kumar
references: Clin Exp Allergy. 2003 May;33(5):688-95
references: 12752600
references: Clin Exp Allergy. 2008 May;38(5):847-56
references: 18307529
references: Thorax. 1998 Oct;53(10):849-56
references: 10193371
references: Am J Respir Cell Mol Biol. 2006 Nov;35(5):565-70
references: 16794258
references: Clin Exp Allergy. 2000 Oct;30(10):1486-92
references: 10998027
references: J Pathol. 2010 Jan;220(2):126-39
references: 19882673
references: J Cell Physiol. 2009 Mar;218(3):467-72
references: 19034913
references: Curr Drug Targets. 2008 Jun;9(6):485-94
references: 18537587
references: Lab Invest. 2002 Apr;82(4):495-504
references: 11950906
references: Am J Respir Cell Mol Biol. 2007 Jan;36(1):8-12
references: 16917074
references: J Immunol. 2010 Feb 15;184(4):1702-9
references: 20083669
references: Am J Respir Cell Mol Biol. 2002 Sep;27(3):267-72
references: 12204888
references: AAPS J. 2010 Mar;12(1):51-60
references: 19937410
references: Int Rev Immunol. 2009;28(6):535-61
references: 19954362
references: Bioessays. 2010 Jul;32(7):599-608
references: 20544733
references: Lab Invest. 2000 May;80(5):655-62
references: 10830775
references: Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18704-9
references: 19843690