Abstract
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 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.
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