ORCID Profile
0000-0001-6629-8418
Current Organisation
University College Cork, Ireland
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Publisher: Wiley
Date: 07-06-2021
DOI: 10.1111/ALL.14953
Publisher: XMLink
Date: 2023
Publisher: Wiley
Date: 12-04-2013
DOI: 10.1016/J.FEBSLET.2013.03.041
Abstract: JAK/STAT signalling is essential for anti-viral immunity, making IFN-α an obvious anti-viral therapeutic. However, many HCV+ patients fail treatment, indicating that the virus blocks successful IFN-α signalling. We found that STAT1 and STAT3 proteins, key components of the IFN-α signalling pathway were reduced in immune cells and hepatocytes from HCV infected patients, and upon HCV expression in Huh7 hepatocytes. However, STAT1 and STAT3 mRNA levels were normal. Mechanistic analysis revealed that in the presence of HCV, STAT3 protein was preferentially ubiquitinated, and degradation was blocked by the proteasomal inhibitor MG132. These findings show that HCV inhibits IFN-α responses in a broad spectrum of cells via proteasomal degradation of JAK/STAT pathway components.
Publisher: Wiley
Date: 31-10-2019
DOI: 10.1111/ALL.14087
Abstract: It is suggested that airway fungi, in particular Aspergillus may impinge on clinical phenotype in asthma. Indeed, the term severe asthma with fungal sensitization (SAFS) has been coined. We aimed to ascertain whether the presence of fungi, in particular Aspergillus fumigatus , in the airway correlated with asthma severity and control. Furthermore, we aimed to determine whether traditional markers of Aspergillus sensitization related to the presence of Aspergillus within the airway. Sixty‐nine patients characterized by asthma severity (GINA) and level of control (ACQ‐7) underwent bronchoscopy and bronchoalveolar lavage (BAL). Serum was assessed for A fumigatus‐ specific IgE and total IgE. Galactomannan and relevant cytokine levels were assessed in serum, plasma and BAL. BAL was analyzed for the presence of A fumigatus. In BAL, fungi were visible by microscopy in 70% and present by qPCR in 86% of patients, while A fumigatus was detectable by qPCR in 46%. Plasma and BAL IL‐4, IL‐6, IL‐10, IL‐13 and TNF‐α correlated with BAL fungal presence, while plasma IL‐17 correlated with BAL fungal presence. Aspergillus positive BAL correlated with increased plasma and BAL IL‐6 and BAL IL‐13. There was no relationship between fungal airway presence and steroid dose, asthma severity or control. The presence of Aspergillus within the airway did not relate to serum IgE positivity for Aspergillus . Fungi were present in a large proportion of our asthmatic patients’ airways, but their presence was not predicted by traditional markers of sensitization, nor did it appear to be related to measures of disease severity or control.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for LIAM FANNING.