MiR-122 induces neutrophilic inflammation in rhinovirus lung infection and asthma exacerbation by targeting SOCS-1 — ASN Events
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  2. Poster Session One & Burnet Oration Cocktail Function
  3. MiR-122 induces neutrophilic inflammation in rhinovirus lung infection and asthma exacerbation by targeting SOCS-1

MiR-122 induces neutrophilic inflammation in rhinovirus lung infection and asthma exacerbation by targeting SOCS-1 (#190)

Adam M Collison 1 , Leon A Sokulsky 1 , Ana Pereira de Siqueria 1 , Matthew Morten 1 , Michael R Edwards 2 , Ross P Walton 2 , Sebastian L Johnston 2 , Nathan W Bartlett 2 3 , Paul S Foster 3 , Joerg Mattes 1 4
  1. Priority Research Centre GrowUpWell® , Experimental and Translational Respiratory Medicine Group, School of Medicine and Public Health, University of Newcastle and Hunter Medical Research Institute, Callaghan, NSW, Australia
  2. Airway Disease Infection Section, National Heart and Lung Institute, Medical Research Council & Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College, London, England
  3. Priority Research Centre for Healthy Lungs, University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW, Australia
  4. Paediatric Respiratory and Sleep Medicine, Newcastle Children's Hospital, Kaleidoscope, Newcastle, NSW, Australia

Introduction: MicroRNAs (miRNAs) are small non-coding RNA molecules that exert posttranscriptional modulation of gene expression. Suppressor of cytokine signalling (SOCS)-1 is a negative regulator of antiviral interferon (IFN) responses and its translation has been demonstrated to be modulated by miR-122 ex-vivo. Here, we investigate a role for miR-122 in rhinovirus (RV) 1B (common cold virus) infection in naïve and allergic mice.

Methods: Naïve BALB/c mice (non-allergic model) or mice sensitised and challenged with house dust mite (HDM; allergic airways inflammation model) were inoculated with infective or UV-inactivated RV intranasally to induce or exacerbate inflammatory and antiviral responses in the lung. Prior to RV infection, some mice were administered antagomirs targeting miR-122 or scrambled antagomirs. In separate experiments, mice were also treated with SOCS-1 silencing or non-sense (si)-RNA along with antagomirs targeting miR-122 or scrambled controls. Inflammation, antiviral responses and airways hyperreactivity (AHR) in response to increased methacholine doses was quantified 24 hours post infection. 

Results: MiR-122 was upregulated by RV infection in immortalized human airway basal cells and in mouse lungs. MiR-122 inhibition reduced neutrophilic lung inflammation, AHR, and CXCL2 (macrophage inflammatory protein 2-alpha) expression in the non-allergic infection and the allergic exacerbation model. Inhibition of miR-122 upregulated SOCS-1 protein expression and concurrent siRNA-mediated targeting of SOCS-1 resulted in a restoration of RV-induced neutrophilic lung inflammation, AHR and CXCL2 expression.

Conclusion: MiR-122 regulates RV-induced neutrophilic airways inflammation and AHR by posttranscriptional regulation of SOCS-1, which may be exploitable as a therapeutic approach for RV-induced lung disease and asthma exacerbations.

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