https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52589 Wed 28 Feb 2024 15:29:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50541 Wed 02 Aug 2023 13:55:11 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46307 Alternaria Alternata (AA)– induced airway inflammation. Methods: PNU-282987 was administered to mice that received recombinant IL-33 or AA intranasal challenges. Lung histological analysis and flow cytometry were performed to determine airway inflammation and the infiltration and activation of ILC2s. The previously published a7nAChR agonist GTS-21 was employed as a comparable reagent. ILC2s were isolated from murine lung tissue and cultured in vitro in the presence of IL-33, IL-2, and IL-7 with/without either PNU-282987 or GTS-21. The expression of the transcription factors GATA3, IKK, and NF-kB were also determined. Results: PNU-282987 and GTS-21 significantly reduced goblet cell hyperplasia in the airway, eosinophil infiltration, and ILC2s numbers in BALF, following IL-33 or AA challenge. In vitro IL-33 stimulation of isolated lung ILC2s showed a reduction of GATA3 and Ki67 in response to PNU-282987 or GTS-21 treatments. There was a significant reduction in IKK and NF-kB phosphorylation in the PNU-282987–treated group when compared to the GTS-21–treated ILC2s. Conclusion: PNU-282987 inhibits ILC2-associated airway inflammation, where its effects were comparable to that of GTS-21.]]> Tue 15 Nov 2022 10:22:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48011 + memory T cells were the predominant sources of interleukin (IL)-4 and IL-13 transcripts whose expressions were dexamethasone resistant. Production of IL-13 by these cells was validated by IL-13-reporter mice. Neutralization of IL-13 abolished HDM/LPS-induced airway hyperresponsiveness, airway inflammation, and decreased mucus hypersecretion. Furthermore, using Ingenuity Pathway Analysis systems, we identified canonical pathways and upstream regulators that regulate the activation of basophils, ILC2, and CD8⁺ memory T cells. Our study provides mechanistic insights and an important reference resource for further understanding of the immune landscape during asthma exacerbation.]]> Thu 23 Mar 2023 10:07:13 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46043 + T cells, and macrophages are significantly elevated in the bronchoalveolar lavage fluid of patients. A set of cytokines and intracellular transduction regulators are associated with asthma exacerbations and are shared across multiple cell clusters, forming a complicated molecular framework. An additional group of core exacerbation-associated modules is activated, including eukaryotic initiation factor 2 signaling, ephrin receptor signaling, and C-X-C chemokine receptor type 4 signaling in the subpopulations of CD8⁺ T cells (C1-a) and monocyte clusters (C7 clusters), which are associated with infection. Conclusion: Our study identified a significant number of severe asthma-associated genes that are differentially expressed by multiple cell clusters.]]> Thu 10 Nov 2022 14:51:33 AEDT ]]>