https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 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:35877 Wed 26 Aug 2020 10:25:47 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24139 Wed 24 Nov 2021 15:51:33 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:16713 Wed 11 Apr 2018 17:02:19 AEST ]]> 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:6954 Wed 11 Apr 2018 13:48:02 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:4347 Wed 11 Apr 2018 11:56:12 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27454 Wed 11 Apr 2018 09:28:10 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:13954 Wed 11 Apr 2018 09:13:08 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35372 Wed 08 Jul 2020 10:53:44 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:26090 Wed 02 Mar 2022 14:26:24 AEDT ]]> 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:49281 Enterovirus genus in the family Picornaviridae. Different RVs bind to one of three known cellular receptors (intercellular adhesion molecule-1, low density lipoprotein receptor, and cadherin-related family member 3) on airway epithelial cells to initiate their replication cycle. Strategies to categorize RVs have been shaped by increased understanding of virus biology and have passed through several iterations since virus discovery in the 1950s. The RVs are currently classified into over 160 types within three species (A, B, and C) based on phylogenetic sequence criteria and distinct genomic features. An understanding of RV structure, replication, and diversity is necessary to develop novel treatment strategies. This chapter will provide an overview of the structural and genetic features that distinguish RV species, as well as methods of RV classification.]]> Tue 14 Nov 2023 14:44:32 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54571 Tue 14 May 2024 14:15:56 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47015 Tue 13 Dec 2022 11:55:35 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:25846 Thu 28 Oct 2021 12:37:11 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:45097 Thu 27 Oct 2022 13:58:29 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29090 Thu 26 Jul 2018 14:43:28 AEST ]]> 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:33763 Thu 17 Feb 2022 09:27:27 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44421 Thu 13 Oct 2022 09:37:29 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:8053 Sat 24 Mar 2018 08:35:04 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10647 Sat 24 Mar 2018 08:13:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17617 Sat 24 Mar 2018 08:01:58 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17943 Sat 24 Mar 2018 07:56:30 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21337 in vitro. Objective: We sought to elucidate the molecular mechanisms by which ß-agonists exert anti-inflammatory effects in allergen-driven and rhinovirus 1B-exacerbated allergic airways disease (AAD). Methods: Mice were sensitized and then challenged with house dust mite to induce AAD while receiving treatment with salmeterol, formoterol, or salbutamol. Mice were also infected with rhinovirus 1B to exacerbate lung inflammation and therapeutically administered salmeterol, dexamethasone, or the PP2A-activating drug (S)-2-amino-4-(4-[heptyloxy]phenyl)-2-methylbutan-1-ol (AAL[S]). Results: Systemic or intranasal administration of salmeterol protected against the development of allergen- and rhinovirus-induced airway hyperreactivity and decreased eosinophil recruitment to the lungs as effectively as dexamethasone. Formoterol and salbutamol also showed anti-inflammatory properties. Salmeterol, but not dexamethasone, increased PP2A activity, which reduced CCL11, CCL20, and CXCL2 expression and reduced levels of phosphorylated extracellular signal-regulated kinase 1 and active nuclear factor κB subunits in the lungs. The anti-inflammatory effect of salmeterol was blocked by targeting the catalytic subunit of PP2A with small RNA interference. Conversely, increasing PP2A activity with AAL(S) abolished rhinovirus-induced airway hyperreactivity, eosinophil influx, and CCL11, CCL20, and CXCL2 expression. Salmeterol also directly activated immunoprecipitated PP2A in vitro isolated from human airway epithelial cells. Conclusions: Salmeterol exerts anti-inflammatory effects by increasing PP2A activity in AAD and rhinovirus-induced lung inflammation, which might potentially account for some of its clinical benefits.]]> Sat 24 Mar 2018 07:52:49 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:5105 Sat 24 Mar 2018 07:48:52 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:5387 Sat 24 Mar 2018 07:43:55 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:32746 Mon 23 Sep 2019 11:49:13 AEST ]]> 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:41043 p=.001), use of inhaled corticosteroids (68.2% and RR 2.17, 95% CI 1.19-3.99, p=.001) and short-acting β-agonists in the last 12 months (95.2% and RR 1.49, 95% CI 1.17-1.89, p=.001), as compared to those with RV negative bronchiolitis and no maternal asthma history. More children in this group had an abnormal airway resistance (33.3% and adjusted risk ratio [aRR] 3.11, 95% CI 1.03-9.47, p=.045) and reactance (27.8% and aRR 2.11, 95% CI 1.06-4.26, p=.035) at 5 Hz, as compared to those with RV negative bronchiolitis and no maternal asthma history. Conclusion: Hospitalization for RV positive bronchiolitis in early life combined with a history of maternal asthma identifies a subgroup of children with a high asthma burden while participants with only one of the two risk factors had intermediate risk for asthma.]]> Mon 08 Aug 2022 14:50:18 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37876 Fri 28 May 2021 12:47:02 AEST ]]> 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:24497 Ex vivo knockdown of these microRNAs restored TLR7 expression with concomitant augmentation of virus-induced IFN production. Conclusions: In severe asthma, TLR7 deficiency drives impaired innate immune responses to virus by AMs. Blocking a group of microRNAs that are up-regulated in these cells can restore antiviral innate responses, providing a novel approach for therapy in asthma.]]> Fri 01 Apr 2022 09:26:07 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33480 -/-) BALB/c mice were infected intranasally with RV1B. In separate experiments, Tnfsf10^-/- mice were sensitized and challenged via the airway route with house dust mite (HDM) to induce allergic airways disease and then challenged with RVIB or UV-RVIB. Airway hyperreactivity (AHR) was invasively assessed as total airways resistance in response to increasing methacholine challenge and inflammation was assessed in bronchoalveolar lavage fluid at multiple time points postinfection. Chemokines were quantified by ELISA of whole lung lysates and viral load was determined by quantitative RT-PCR and tissue culture infective dose (TCID₅₀). Human airway epithelial cells (BEAS2B) were infected with RV1B and stimulated with recombinant TRAIL or neutralizing anti-TRAIL antibodies and viral titer assessed by TCID₅₀. HDM-challenged Tnfsf10 ^-/- mice were protected against RV-induced AHR and had suppressed cellular infiltration in the airways upon RV infection. Chemokine C-X-C-motif ligand 2 (CXCL2) production was suppressed in naïve Tnfsf10^-/- mice infected with RV1B, with less RV1B detected 24 h postinfection. This was associated with reduced apoptotic cell death and a reduction of interferon (IFN)-λ2/3 but not IFN-α or IFN-β. TRAIL stimulation increased, whereas anti-TRAIL antibodies reduced viral replication in RV1B-infected BEAS2B cells in vitro. In conclusion, TRAIL promotes RV-induced AHR, inflammation and RV1B replication, implicating this molecule and its downstream signaling pathways as a possible target for the amelioration of RV1B-induced allergic and nonallergic lung inflammation and AHR.]]> Fri 01 Apr 2022 09:25:03 AEDT ]]>