https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47470 Wed 24 Jan 2024 15:57:20 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32103 Wed 17 Nov 2021 16:28:21 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46351 n = 115) and Perth (n = 30), Australia. The Newcastle cohort was enriched with people with asthma (n = 37) and COPD (n = 38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC. Results: Increased gene expression of ACE2 was associated with older age (P = 0.03) and male sex (P = 0.03), but not with pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma patients (P = 0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in patients with asthma (P = 0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface, was increased (P = 0.02). ACE2 protein expression was also reduced in endobronchial biopsies from asthma patients. Conclusion: Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications.]]> Tue 15 Nov 2022 15:15:58 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23653 Thu 28 Oct 2021 13:04:17 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39986 Thu 21 Jul 2022 10:44:03 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25872 in vitro. The significantly lower levels seen in asthmatic pAEC subsequently contributes to the dysregulated repair observed in these cells.]]> Thu 20 Aug 2020 08:48:26 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25955 non-CF and pAEC_CF, respectively) during exposure to physiologically relevant NE. The effect of NE activity on pAEC_CF wound repair was also assessed. We report that viability after 48 hours was significantly decreased by 100 nM NE in pAEC_non-CF and pAEC_CF owing to rapid cellular detachment that was accompanied by inflammatory cytokine release. Furthermore, both phenotypes initiated an apoptotic response to 100 nM NE, whereas ≥50 nM NE activity significantly inhibited the proliferative capacity of cultures. Similar concentrations of NE also significantly inhibited wound repair of pAEC_CF, but this effect was reversed by the addition of α1AT. Collectively, our results demonstrate free NE activity is deleterious for epithelial homeostasis and support the hypothesis that proteases in the airway contribute directly to CF structural lung disease. Our results also highlight the need to investigate antiprotease therapies in early CF disease in more detail.]]> Thu 04 Nov 2021 10:39:27 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26099 TM Western assays. Transepithelial permeability assays were performed to assess effects on barrier functionality. RT2 Profiler focused qPCR arrays and pathway analysis evaluating associations between human TJ and antiviral response were performed to identify potential interactions and pathways between genes of interests. Results: HRV-1B infection affected viability that was both time and TCID⁵⁰ dependent. Significant increases in apoptosis and viral replication post-infection correlated with viral titer. Viral infection significantly decreased claudin-1 protein expression at the lower TCID⁵⁰, while a significant decrease in all three TJ protein expressions occurred at higher TCID⁵⁰. Decrease in protein expression was concomitant with significant increases in epithelial permeability of fluorescein isothiocynate labeled-dextran 4 and 20 kDa. Analysis of focused qPCR arrays demonstrated a significant decrease in ZO-1 gene expression. Furthermore, network analysis between human TJ and antiviral response genes revealed possible interactions and regulation of TJ genes via interleukin (IL)-15 in response to HRV-1B infection. Conclusion: HRV-1B infection directly alters human airway epithelial TJ expression leading to increased epithelial permeability potentially via an antiviral response of IL-15.]]> Sat 24 Mar 2018 07:39:52 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28201 Sat 24 Mar 2018 07:23:53 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45191 Mon 29 Jan 2024 17:58:16 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53196 Fri 17 Nov 2023 11:32:25 AEDT ]]>