TY - JOUR T1 - The role of suppressor of cytokine signalling 1 (SOCS1) in virus-induced asthma exacerbations JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2016.PA2611 VL - 48 IS - suppl 60 SP - PA2611 AU - Kate Strong AU - Peter McErlean AU - Jaideep Dhariwal AU - Maria-Belen Trujillo-Torralbo AU - Sebastian L. Johnston AU - Paul Lavender AU - Michael R. Edwards Y1 - 2016/09/01 UR - http://erj.ersjournals.com/content/48/suppl_60/PA2611.abstract N2 - Rationale: Asthma exacerbations are frequently caused by respiratory viral infection, likely due to impaired antiviral interferon induction by asthmatic bronchial epithelial cells (BECs). SOCS1 negatively regulates interferon production and signalling and is induced in response to Th2 cytokines and viral infection.Hypothesis: SOCS1 transcription is increased in asthmatic BECs. Induction of SOCS1 by Th2 cytokines and viruses are mediated via distinct mechanisms.Methods: SOCS1 and interferon-λ1 mRNA induction was measured following ex vivo RV infection of BECs obtained from atopic asthmatics (AA) and non-atopic non-asthmatics (NANA) via qPCR (n=8 of each). The SOCS1 promoter was investigated for transcriptional regulatory activity using luciferase reporter assays in BEAS-2B cells. The histone environment surrounding the human SOCS1 locus was characterised by ChIP-sequencing.Results: SOCS1 mRNA was increased in AA (p<0.01) following RV16 and RSV infection, but not in NANA controls. Two areas of H3K27ac enrichment, indicative of transcriptional regulatory capacity, were identified in the SOCS1 locus; one proximal to the TATA box, and a second distal site 40kb upstream to the SOCS1 transcriptional start site. The proximal SOCS1 promoter was activated in response to IL-4 and IL-13 (p<0.001 versus medium control), likely due to STAT6 binding sites. No proximal promoter activation was seen following RV or RSV infection, despite increased SOCS1 mRNA induction.Conclusions: These data support a role for SOCS1 in virus-induced asthma exacerbations. We are currently investigating the distal enhancer as a potential mediator of virus-induced SOCS1 expression. ER -