https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47737 Wed 25 Jan 2023 15:07:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33081 -/-) mice, one with a targeted deletion and another mutant expressing an major histocompatibility complex (MHC) transgene. To determine the importance of RelB in DCs, RelB-sufficient DCs (RelB^-/- or RelB^-/-) were adoptively transferred into RelB^-/- mice. Both strains had increased pulmonary inflammation compared to their respective wild-type (RelB^-/-) and heterozygous (RelB^-/-) controls. RelB^-/- mice also had increased inflammatory cell influx into the airways, levels of chemokines (CCL2/3/4/5/11/17, CXCL9/10/13) and Th2-associated cytokines (IL-4/5) in lung tissues, serum IgE and airway remodelling (mucus secreting cell numbers (MSCs), collagen deposition and epithelial thickening). Transfer of RelB^-/- CD11c⁺ DCs to RelB^-/- mice decreased pulmonary inflammation, with reduced lung chemokine and Th2-associated cytokine (IL-4/5/13/25/33, thymic stromal lymphopoietin) levels, serum IgE, numbers of type 2 innate lymphoid cells, myeloid DCs, γδ T cells and lung Vß13⁺ T cells, MSCs, airway collagen deposition and epithelial thickening.These data indicate that RelB deficiency may be a key pathway underlying AAI and that DC-encoded RelB is sufficient to restore control.]]> Wed 02 Mar 2022 14:25:08 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16917 Tue 31 Jul 2018 16:15:02 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54156 Tue 06 Feb 2024 12:11:30 AEDT ]]> https://nova.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://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46730 Thu 01 Dec 2022 10:28:14 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14649 Sat 24 Mar 2018 08:20:54 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14650 Sat 24 Mar 2018 08:20:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14651 Sat 24 Mar 2018 08:20:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13324 Sat 24 Mar 2018 08:17:00 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11495 Sat 24 Mar 2018 08:10:23 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11110 Sat 24 Mar 2018 08:10:16 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16920 Sat 24 Mar 2018 08:00:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16915 10) activates the nucleotide-binding domain, leucine-rich repeat protein (NLRP) 3 inflammasome in human airway epithelial cells. Our objective was to determine the innate and adaptive immune responses mediated by the airway epithelium NLRP3 inflammasome in response to PM₁₀ exposure. Using in vitro cultures of human airway epithelial cells and in vivo studies with wild-type and Nlrp3^-/- mice, we investigated the downstream consequences of PM₁₀-induced NLPR3 inflammasome activation on cytokine production, cellular inflammation, dendritic cell activation, and PM₁₀-facilitated allergic sensitization. PM₁₀ activates an NLRP3 inflammasome/IL-1 receptor I (IL-1RI) axis in airway epithelial cells, resulting in IL-1β, CC chemokine ligand-20, and granulocyte/macrophage colony–stimulating factor production, which is associated with dendritic cell activation and lung neutrophilia. Despite these profound innate immune responses in the airway epithelium, the NLRP3 inflammasome/IL-1RI axis is dispensable for PM₁₀-facilitated allergic sensitization. We demonstrate the importance of the lung NLRP3 inflammasome in mediating PM₁₀ exposure–associated innate, but not adaptive, immune responses. Our study highlights a mechanism by which PM₁₀ exposure can contribute to the exacerbation of airway disease, but not PM₁₀-facilitated allergic sensitization.]]> Sat 24 Mar 2018 07:58:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5638 Sat 24 Mar 2018 07:44:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26091 Sat 24 Mar 2018 07:39:54 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41052 Mon 08 Aug 2022 14:57:26 AEST ]]>