The role of interferon in the development of pulmonary arterial hypertension
Interferons (IFNs) are an integral part of the innate immune response to viral infection. As well as possessing important anti-viral properties, they possess immunomodulatory, cytotoxic and anti-tumoural functions. As a consequence, the IFNs (mainly type I IFN) have been utilised for the treatment o...
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ndltd-bl.uk-oai-ethos.bl.uk-6664852016-08-04T03:44:52ZThe role of interferon in the development of pulmonary arterial hypertensionGeorge, Peter MichaelMitchell, Jane; Johnston, Sebastian; Hansel, Trevor2014Interferons (IFNs) are an integral part of the innate immune response to viral infection. As well as possessing important anti-viral properties, they possess immunomodulatory, cytotoxic and anti-tumoural functions. As a consequence, the IFNs (mainly type I IFN) have been utilised for the treatment of human disease where they represent important therapies, most commonly in the treatment of chronic hepatitis C virus (HCV). However, there is now emerging evidence of an association between type I IFN drug treatment and the development of severe and at times irreversible pulmonary arterial hypertension (PAH). Through the course of this PhD I have investigated potential mechanisms for type I IFN induced PAH and have identified the IFN regulated protein IP10 and the promitogen and vasoconstrictor endothelin (ET)-1 as important candidate mediators. It is well established that autoimmune conditions such as systemic sclerosis, where PAH is a common complication, are typified by chronic activation of type I IFN pathways. I have used the observation that IFN drug treatment may cause PAH, as a platform to hypothesise that endogenous type I IFN production may be important in the pathogenesis of systemic sclerosis associated PAH. Through a comprehensive approach utilising in vitro cell culture models, in vivo animal models of disease and patient samples, I have demonstrated that endogenously produced type I IFN plays an important role in the development of systemic sclerosis associated PAH and also idiopathic PAH. I have also gone on to show that other facets of the immune system appear to have pathogenic relevance in this devastating and still under-characterised disease. I conclude that a dysregulated and chronically active innate immune system plays a pathological role in the development of pulmonary arterial hypertension.610Imperial College Londonhttp://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.666485http://hdl.handle.net/10044/1/26116Electronic Thesis or Dissertation |
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610 George, Peter Michael The role of interferon in the development of pulmonary arterial hypertension |
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Interferons (IFNs) are an integral part of the innate immune response to viral infection. As well as possessing important anti-viral properties, they possess immunomodulatory, cytotoxic and anti-tumoural functions. As a consequence, the IFNs (mainly type I IFN) have been utilised for the treatment of human disease where they represent important therapies, most commonly in the treatment of chronic hepatitis C virus (HCV). However, there is now emerging evidence of an association between type I IFN drug treatment and the development of severe and at times irreversible pulmonary arterial hypertension (PAH). Through the course of this PhD I have investigated potential mechanisms for type I IFN induced PAH and have identified the IFN regulated protein IP10 and the promitogen and vasoconstrictor endothelin (ET)-1 as important candidate mediators. It is well established that autoimmune conditions such as systemic sclerosis, where PAH is a common complication, are typified by chronic activation of type I IFN pathways. I have used the observation that IFN drug treatment may cause PAH, as a platform to hypothesise that endogenous type I IFN production may be important in the pathogenesis of systemic sclerosis associated PAH. Through a comprehensive approach utilising in vitro cell culture models, in vivo animal models of disease and patient samples, I have demonstrated that endogenously produced type I IFN plays an important role in the development of systemic sclerosis associated PAH and also idiopathic PAH. I have also gone on to show that other facets of the immune system appear to have pathogenic relevance in this devastating and still under-characterised disease. I conclude that a dysregulated and chronically active innate immune system plays a pathological role in the development of pulmonary arterial hypertension. |
author2 |
Mitchell, Jane; Johnston, Sebastian; Hansel, Trevor |
author_facet |
Mitchell, Jane; Johnston, Sebastian; Hansel, Trevor George, Peter Michael |
author |
George, Peter Michael |
author_sort |
George, Peter Michael |
title |
The role of interferon in the development of pulmonary arterial hypertension |
title_short |
The role of interferon in the development of pulmonary arterial hypertension |
title_full |
The role of interferon in the development of pulmonary arterial hypertension |
title_fullStr |
The role of interferon in the development of pulmonary arterial hypertension |
title_full_unstemmed |
The role of interferon in the development of pulmonary arterial hypertension |
title_sort |
role of interferon in the development of pulmonary arterial hypertension |
publisher |
Imperial College London |
publishDate |
2014 |
url |
http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.666485 |
work_keys_str_mv |
AT georgepetermichael theroleofinterferoninthedevelopmentofpulmonaryarterialhypertension AT georgepetermichael roleofinterferoninthedevelopmentofpulmonaryarterialhypertension |
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