https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48714 Wed 29 Mar 2023 17:10:48 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38040 Wed 28 Jul 2021 10:17:50 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45003 n = 19), including 7 with NEA and healthy controls (n = 10) underwent a clinical assessment, venepuncture and sputum induction. MDMs were co-cultured with apoptotic granulocytes isolated from healthy donors with or without exogenous recombinant galectin-3 (50 μg/mL) and efferocytosis was assessed by flow cytometry. Galectin-3 expression and localisation in MDMs was visualised by immunofluorescence staining and fluorescence microscopy. Galectin-3, interleukin (IL)-6 and CXCL8 secretion were measured in cell culture supernatants by ELISA and cytometric bead array. Results: Baseline efferocytosis (mean (±standard deviation)) was lower in participants with asthma (33.2 (±17.7)%) compared with healthy controls (45.3 (±15.9)%; p = 0.081). Efferocytosis did not differ between the participants with eosinophilic asthma (EA) (31.4 (±19.2)%) and NEA (28.7 (±21.5)%; p = 0.748). Addition of galectin-3 significantly improved efferocytosis in asthma, particularly in NEA (37.8 (±18.1)%) compared with baseline (30.4 (±19.7)%; p = 0.012). Efferocytosis was not associated with any of the clinical outcomes but was negatively correlated with sputum macrophage numbers (Spearman r = − 0.671; p = 0.017). Galectin-3 was diffusely distributed in most MDMs but formed punctate structures in 5% of MDMs. MDM galectin-3 secretion was lower in asthma (9.99 (2.67, 15.48) ng/mL) compared with the healthy controls (20.72 (11.28, 27.89) ng/mL; p = 0.044) while IL-6 and CXCL8 levels were similar. Conclusions: Galectin-3 modulates macrophage function in asthma, indicating a potential role for galectin-3 to reverse impaired efferocytosis in NEA.]]> Wed 26 Oct 2022 09:42:24 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49965 Wed 21 Jun 2023 11:57:33 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48369 Fbln1c-deficient (Fbln1c^–/–) mice had reduced pulmonary remodeling/fibrosis and improved lung function after bleomycin challenge. Fbln1c interacted with fibronectin, periostin, and tenascin-C in collagen deposits following bleomycin challenge. In a potentially novel mechanism of fibrosis, Fbln1c bound to latent TGF-β–binding protein 1 (LTBP1) to induce TGF-β activation and mediated downstream Smad3 phosphorylation/signaling. This process increased myofibroblast numbers and collagen deposition. Fbln1c and LTBP1 colocalized in lung tissues from patients with IPF. Thus, Fbln1c may be a novel driver of TGF-β–induced fibrosis involving LTBP1 and may be an upstream therapeutic target.]]> Wed 15 Mar 2023 13:12:38 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19108 Wed 11 Apr 2018 16:00:33 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27945 Puma-dependent neuronal apoptosis. Of particular importance to the developing brain is the direct NMDAR-dependent transcriptional control of glutathione biosynthesis, disruption of which can lead to degeneration. Notably, these activity-dependent cell-autonomous mechanisms were found to cooperate with non-cell-autonomous Nrf2-driven support from astrocytes to maintain neuronal GSH levels in the face of oxidative insults. Thus, developmental NMDAR hypofunction and glutathione system deficits, separately implicated in several neurodevelopmental disorders, are mechanistically linked.]]> Wed 11 Apr 2018 14:57:38 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34558 Wed 10 Nov 2021 15:14:18 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36433 + neutrophils as median fluorescence intensity (MFI). Results: Neutrophil surface expression of CD62L was significantly reduced in COPD (median (IQR) MFI: 1156 (904, 1365)) compared with asthma (1865 (1157, 2408)) and healthy controls (2079 (1054, 2960)); p=0.028. COPD neutrophils also demonstrated a significant reduction in CD62L expression with and without fMLF stimulation. Asthma participants had a significantly increased proportion and number of CD62L^bright/CD16^dim neutrophils (median: 5.4% and 0.14 x 10⁹/L, respectively), in comparison with healthy (3.54% and 0.12 x 10⁹/L, respectively); p<0.017. Conclusion: Reduced CD62L expression suggests blood neutrophils have undergone priming in COPD but not in asthma, which may be the result of systemic inflammation. The increased shedding of CD62L receptor by COPD blood neutrophils suggests a high sensitivity for activation]]> Wed 10 Nov 2021 15:05:07 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44806 Wed 01 May 2024 12:05:04 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47641 Tue 24 Jan 2023 14:38:00 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53957 Tue 23 Jan 2024 10:53:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46094 1 and FVC. Trends towards similar clinical associations with elevated MCs were observed in a paucigranulocytic subpopulation (n = 15) lacking airway eosinophilia or neutrophilia. Receiver operator characteristic (ROC) analysis showed peripheral blood eosinophil (PBE) count predicted elevated sputum eosinophils and basophils, but not MCs. Conclusions and Clinical Relevance: Sputum MCs are elevated in asthma, and their measurement may be useful as they relate to key clinical features of asthma (spirometry, asthma control, AHR). PBE count did not predict airway MC status, suggesting direct measurement of airway MCs by sensitive methods such as flow cytometry should be further developed.]]> Tue 21 May 2024 11:55:14 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48579 Tue 21 Mar 2023 17:43:58 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43418 Tue 20 Sep 2022 08:26:35 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49105 Tue 14 Nov 2023 14:40:06 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43823 Tue 04 Oct 2022 11:04:24 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36051 Thu 28 Oct 2021 13:04:53 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45375 Thu 27 Oct 2022 16:54:22 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30788 Thu 27 Jan 2022 15:58:12 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46113 n = 12, defined as per GINA criteria), non-severe uncontrolled (n = 21) and controlled asthma (n = 21) and healthy controls (n = 15). Sputum RNA was extracted and transcriptomic profiles were generated (Illumina HumanRef-8 V2) and analysed (GeneSpring). Sputum protein lysates were analysed for p38 activation in a validation study (n = 24 asthma, n = 8 healthy) by western blotting. Results: There were 2166 genes differentially expressed between the four groups. In severe asthma, the expression of 1875, 1308 and 563 genes was altered compared to healthy controls, controlled and uncontrolled asthma, respectively. Of the 1875 genes significantly different to healthy controls, 123 were >2-fold change from which four networks were identified. Thirty genes (>2-fold change) were significantly different in severe asthma compared to both controlled asthma and healthy controls. There was enrichment of genes in the p38 signalling pathway that were associated with severe asthma. Phosphorylation of p38 was increased in a subset of severe asthma samples, correlating with neutrophilic airway inflammation. Conclusion: Severe asthma is associated with substantial differences in sputum gene expression that underlie unique cellular mechanisms. The p38 signalling pathway may be important in the pathogenesis of severe asthma, and future investigations into p38 inhibition are warranted as a ‘non-Th2’ therapeutic option.]]> Thu 18 Apr 2024 11:56:00 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34597 Thu 13 Jan 2022 10:31:31 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49306 Thu 11 May 2023 14:32:33 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52202 Thu 05 Oct 2023 10:09:05 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20434 −/− C57BL/6 mouse line. The resulting animals exhibited no obvious developmental abnormality, contained normal numbers of granulated MCs in their tissues, and did not compensate for their loss of the membrane tryptase by increasing their expression of other granule proteases. When Prss31-null MCs were activated with a calcium ionophore or by their high affinity IgE receptors, they degranulated in a pattern similar to that of WT MCs. Prss31-null mice had increased baseline airway reactivity to methacholine but markedly reduced experimental chronic obstructive pulmonary disease and colitis, thereby indicating both beneficial and adverse functional roles for the tryptase. In a cigarette smoke-induced model of chronic obstructive pulmonary disease, WT mice had more pulmonary macrophages, higher histopathology scores, and more fibrosis in their small airways than similarly treated Prss31-null mice. In a dextran sodium sulfate-induced acute colitis model, WT mice lost more weight, had higher histopathology scores, and contained more Cxcl-2 and IL-6 mRNA in their colons than similarly treated Prss31-null mice. The accumulated data raise the possibility that inhibitors of this membrane tryptase may provide additional therapeutic benefit in the treatment of humans with these MC-dependent inflammatory diseases.]]> Sat 24 Mar 2018 08:03:21 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:16896 Sat 24 Mar 2018 07:58:48 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28633 Sat 24 Mar 2018 07:38:53 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25871 Sat 24 Mar 2018 07:25:52 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:55409 Mon 27 May 2024 12:11:12 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47276 Mon 27 Mar 2023 13:58:24 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46232 Mon 14 Nov 2022 12:33:10 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:55080 Mon 08 Apr 2024 14:10:40 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49427 Fri 12 May 2023 15:16:07 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38377 Fri 10 Sep 2021 12:38:35 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37118 Fri 03 Dec 2021 10:32:20 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33085 -/-) and TLR4-deficient (Tlr4^-/-) mice. CS-induced airway fibrosis, characterized by increased collagen deposition around small airways, was not altered in Tlr2^-/- mice but was attenuated in Tlr4^-/- mice compared with CS-exposed WT controls. However, Tlr2^-/- mice had increased CS-induced emphysema-like alveolar enlargement, apoptosis, and impaired lung function, while these features were reduced in Tlr4^-/- mice compared with CS-exposed WT controls. Taken together, these data highlight the complex roles of TLRs in the pathogenesis of COPD and suggest that activation of TLR2 and/or inhibition of TLR4 may be novel therapeutic strategies for the treatment of COPD.]]> Fri 01 Apr 2022 09:24:33 AEDT ]]>