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Title: The role of suppressors of cytokine signalling in asthma
Author: Doran , Emma Clare
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2013
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The suppressors of cytokine signalling (SOCS) are a family of molecules implicated in the crucial regulation of the Janus kinase (JAK) - signal transducers and activators of transcription (STAT) pathway. SOCS have been shown to attenuate inflammation in a negative feedback manner. Chronic inflammation has been identified within the airways of asthmatic patients, leading to the development of severe disease. The main aim of this study was to investigate SOCS! , SOCS2 and SOCS3 expression within the asthmatic airways. A particular emphasis was focused on severe asthmatics who suffer from poorly controlled disease. investigation of SOCS molecules in in vivo mouse models of allergic disease showed the absence of SOCS2 led to increased levels of SOCS3 and this was associated with exacerbated disease. Investigation of SOCS expression in bronchial biopsies from healthy controls, mild/moderate asthmatics and severe asthmatics found SOCS1 mRNA expression was significantly reduced in the airways of severe asthma patients. Stratification of patients showed asthmatics receiving high dose steroids and those with persistent eosinophilic inflammation within their airways had significantly decreased SOCS 1 mRNA expression. Immunohistochemistry carried out on. a subset of patients identified localisation of SOCS 1 to the airway epithelium. In vitro investigation using a bronchial epithelial cell line showed induction of SOCS1 in response to IL-13 and dexamethasone. Investigation into the effects of chronic steroid exposure on bronchial epithelial cells showed inhibition of SOCS 1 expression with partial rescue when steroid was removed from the system. In conclusion, differential SOCS1 expression is associated with a distinct inflammatory subtype of severe asthma patients; this may have important consequences for the treatment of these poorly controlled asthmatics .
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available