https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42351 Wed 30 Aug 2023 15:15:14 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50840 Wed 28 Feb 2024 16:33:00 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50653 Wed 28 Feb 2024 15:55:38 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45152 Wed 26 Oct 2022 13:51:48 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44978 Wed 26 Oct 2022 08:53:24 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22168 -/-) BALB/c mice were intranasally sensitised and challenged with HDM prior to infection with RV1B. In some experiments, mice were administered recombinant IFN or adoptively transferred with plasmacytoid dendritic cells (pDC). Results: Allergic Tlr7^-/- mice displayed impaired IFN release upon RV1B infection, increased virus replication and exaggerated eosinophilic inflammation and airways hyper reactivity. Treatment with exogenous IFN or adoptive transfer of TLR7-competent pDCs blocked these exaggerated inflammatory responses and boosted IFNγ release in the absence of host TLR7 signalling. TLR7 expression in the lungs was suppressed by allergic inflammation and by interleukin (IL)-5-induced eosinophilia in the absence of allergy. Subjects with moderate-to-severe asthma and eosinophilic but not neutrophilic airways inflammation, despite inhaled steroids, showed reduced TLR7 and IFNλ2/3 expression in endobronchial biopsies. Furthermore, TLR7 expression inversely correlated with percentage of sputum eosinophils. Conclusions: This implicates IL-5-induced airways eosinophilia as a negative regulator of TLR7 expression and antiviral responses, which provides a molecular mechanism underpinning the effect of eosinophil-targeting treatments for the prevention of asthma exacerbations.]]> Wed 11 Apr 2018 15:36:21 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38147 Wed 04 Aug 2021 18:45:51 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35004 Wed 02 Mar 2022 14:28:06 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49742 Tue 30 May 2023 15:22:46 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47290 Tue 30 Apr 2024 08:50:07 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48671 Tue 28 Mar 2023 10:25:49 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50423 Tue 25 Jul 2023 18:33:24 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43133 Tue 13 Sep 2022 15:14:32 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54163 Tue 06 Feb 2024 13:06:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45554 Muc5ac-deficient (Muc5ac^–/–) mice had attenuated RV-induced (RV-induced) airway inflammation, and exogenous MUC5AC glycoprotein administration augmented inflammatory responses and increased the release of extracellular adenosine triphosphate (ATP) in mice and human airway epithelial cell cultures. Hydrolysis of ATP suppressed MUC5AC augmentation of RV-induced inflammation in mice. Therapeutic suppression of mucin production using an EGFR antagonist ameliorated immunopathology in a mouse COPD exacerbation model. The coordinated virus induction of MUC5AC and MUC5B expression suggests that non-Th2 mechanisms trigger mucin hypersecretion during exacerbations. Our data identified a proinflammatory role for MUC5AC during viral infection and suggest that MUC5AC inhibition may ameliorate COPD exacerbations.]]> Tue 01 Nov 2022 11:18:46 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45548 Tue 01 Nov 2022 11:07:41 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27734 Thu 28 Oct 2021 13:04:05 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37877 Thu 28 Oct 2021 13:02:25 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45347 Thu 27 Oct 2022 17:08:36 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45297 Thu 27 Oct 2022 15:02:18 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38505 Thu 18 Nov 2021 09:58:18 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34955 Thu 17 Feb 2022 09:32:05 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33763 Thu 17 Feb 2022 09:27:27 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40298 Thu 11 May 2023 14:03:27 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46730 Thu 01 Dec 2022 10:28:14 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27733 Sat 24 Mar 2018 07:36:43 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22271 Sat 24 Mar 2018 07:17:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22024 Sat 24 Mar 2018 07:15:46 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38585 in vitro airway epithelial infection models using high multiplicity of infection (MOI) and lacking genome-wide, time course analyses have obscured the role of epithelial innate anti-viral immunity in asthma and COPD. To address this, we developed a low MOI rhinovirus model of differentiated primary epithelial cells obtained from healthy, asthma and COPD donors. Using genome-wide gene expression following infection, we demonstrated that gene expression patterns are similar across patient groups, but that the kinetics of induction are delayed in cells obtained from asthma and COPD donors. Rhinovirus-induced innate immune responses were defined by interferons (type-I, II, and III), interferon response factors (IRF₁, IRF₃, and IRF₇), TLR signaling and NF-κB and STAT₁ activation. Induced gene expression was evident at 24 h and peaked at 48 h post-infection in cells from healthy subjects. In contrast, in cells from donors with asthma or COPD induction was maximal at or beyond 72–96 h post-infection. Thus, we propose that propensity for viral exacerbations of asthma and COPD relate to delayed (rather than deficient) expression of epithelial cell innate anti-viral immune genes which in turns leads to a delayed and ultimately more inflammatory host immune response.]]> Mon 29 Jan 2024 18:03:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38861 Streptococcus pneumoniae, mechanistically through inhibition of the antimicrobial peptide (AMP) cathelicidin. Using experiments in human cells and mouse infection models, we performed a head-to-head comparison of the effects of the major ICS agents used in COPD on innate immunity.]]> Mon 29 Jan 2024 17:53:07 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42308 Camp^-/-) and exogenous cathelicidin prevented ICS-mediated expansion of streptococci within the microbiota and improved bacterial clearance. Suppression of pulmonary immunity by ICS was mediated by augmentation of the protease cathepsin D. Collectively, these data suggest a central role for cathepsin D/cathelicidin in the suppression of antibacterial host defense by ICS in COPD. Therapeutic restoration of cathelicidin to boost antibacterial immunity and beneficially modulate the lung microbiota might be an effective strategy in COPD.]]> Mon 22 Aug 2022 10:35:15 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54768 Mon 11 Mar 2024 15:08:11 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41052 Mon 08 Aug 2022 14:57:26 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45262 p=<0.0001) by up to a 24 fold (96% reduction) and in nasal wash (p=0.0107) up to a 15 fold (93% reduction) in comparison to untreated animals. Interpretation: The results of our study support clinical development of a therapy based on prophylactic TLR2/6 innate immune activation in the URT, to reduce SARS-CoV-2 transmission and provide protection against COVID-19.]]> Fri 28 Oct 2022 11:45:44 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42174 2⁻) production in senescent fibroblasts. Targeting STAT3 activity using the small-molecule inhibitor STA-21 attenuated IL-6 production, reduced p21 levels, decreased senescence-associated β-galactosidase accumulation, and restored normal mitochondrial function. The results of this study illustrate that stress-induced senescence in lung fibroblasts involves the activation of STAT3, which can be pharmacologically modulated.]]> Fri 26 Aug 2022 08:10:19 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51957 Fri 22 Sep 2023 17:07:03 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46061 in vitro in human airway epithelial cell cultures and in vivo in mouse models of ICS administration. Mice deficient in the type I IFN-α/β receptor (Ifnar1^-/-) and administration of exogenous IFN-β were used to study the functional role of type-I interferon signaling in ACE2 expression. We compared sputum ACE2 expression in patients with COPD stratified according to use or nonuse of ICS. Results: ICS administration attenuated ACE2 expression in mice, an effect that was reversed by exogenous IFN-β administration, and Ifnar1^-/- mice had reduced ACE2 expression, indicating that type I interferon contributes mechanistically to this effect. ICS administration attenuated expression of ACE2 in airway epithelial cell cultures from patients with COPD and in mice with elastase-induced COPD-like changes. Compared with ICS nonusers, patients with COPD who were taking ICSs also had reduced sputum expression of ACE2. Conclusion: ICS therapies in COPD reduce expression of the SARS-CoV-2 entry receptor ACE2. This effect may thus contribute to altered susceptibility to COVID-19 in patients with COPD.]]> Fri 11 Nov 2022 14:22:05 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51239 Fri 10 Nov 2023 07:15:55 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41554 Fri 05 Aug 2022 14:23:21 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37697 Fri 01 Apr 2022 09:26:23 AEDT ]]>