https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 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:53765 Wed 28 Feb 2024 15:59:45 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52054 Wed 27 Sep 2023 15:30:47 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40357 Wed 27 Jul 2022 15:15:01 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45172 Wed 26 Oct 2022 14:18:41 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45076 ELN gene expression in tumors from CRC patients and adjacent non-tumor colon tissues and healthy controls from two existing microarray datasets. ELN protein was measured in human normal colon cells and colon cancer epithelial cells and tumor development was assessed in colon epithelial cells cultured in medium with or without ELN peptide on plates coated with ELN recombinant protein. Control plates were coated with PBS only. Results: We found ELN gene expression was increased in tumors from CRC patients compared to adjacent non-tumor tissues and healthy controls. ELN protein was increased in cancer cells compared to normal colon epithelial cells. Transforming growth factor beta (TGF-β) was a key cytokine to induce production of ECM proteins, but it did not induce ELN expression in colon cancer cells. Matrix metalloproteinase 9 (MMP9) gene expression was increased, but that of MMP12 (elastase) did not change between CRC patients and control. Tissue inhibitor of metalloproteinases 3 (TIMP3) gene expression was decreased in colon tissues from CRC patients compared to healthy controls. However, MMP9, MMP12 and TIMP3 proteins were increased in colon cancer cells. ELN recombinant protein increased proliferation and wound healing in colon cancer epithelial cells. This had further increased in cancer cells incubated in plates coated with recombinant ELN coated plate and in culture media containing ELN peptide. A potential mechanism was that ELN induced epithelial mesenchymal transition with increased alpha-smooth muscle actin and vimentin proteins but decreased E-cadherin protein. Tumor necrosis factor alpha (TNF) mRNA was also increased in CRC patients compared to controls. ELN recombinant protein induced further increases in TNF protein in mouse bone marrow derived macrophages after lipopolysaccharide stimulation. Conclusions: These data suggest ELN regulates tumor development and the microenvironment in CRC.]]> Wed 26 Oct 2022 12:30:48 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47737 Wed 25 Jan 2023 15:07:49 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:11267 Wed 24 Jul 2013 22:28:44 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43527 Wed 21 Sep 2022 11:32:49 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37130 Wed 19 Aug 2020 12:59:44 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38204 Wed 18 Aug 2021 09:53:13 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36606 Wed 17 Nov 2021 16:31:32 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21992 Bacillus species were identified compared with healthy controls. PCR analyses revealed increased rates of detection of potentially pathogenic bacteria with Haemophilus influenzae detection associated with higher sputum levels of NE and IL-1β, while Streptococcus pneumoniae was more common in male ex-smokers with emphysema and a deficit in diffusion capacity. Conclusion: Non-pathogenic and pathogenic bacteria were altered in the sputum of patients with COPD. These observations highlight the potential to identify treatment and management strategies that both target specific bacterial pathogens and restore the microbial balance, which may lead to reductions in inflammation and subsequent improvements in lung health.]]> Wed 17 Nov 2021 16:31:05 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36824 Wed 17 Nov 2021 16:29:09 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38603 Chlamydia trachomatis infection is a primary cause of reproductive tract diseases including infertility. Previous studies showed that this infection alters physiological activities in mouse oviducts. Whether this occurs in the uterus and cervix has never been investigated. This study characterized the physiological activities of the uterine horn and the cervix in a Chlamydia muridarum (Cmu)-infected mouse model at three infection time points of 7, 14, and 21 days postinfection (dpi). Cmu infection significantly decreased contractile force of spontaneous contraction in the cervix (7 and 14 dpi; P < 0.001 and P < 0.05, respectively), but this effect was not observed in the uterine horn. The responses of the uterine horn and cervix to oxytocin were significantly altered by Cmu infection at 7 dpi (P < 0.0001), but such responses were attenuated at 14 and 21 dpi. Cmu infection increased contractile force to prostaglandin (PGF2_α) by 53–83% in the uterine horn. This corresponded with the increased messenger ribonucleic acid (mRNA) expression of Ptgfr that encodes for its receptor. However, Cmu infection did not affect contractions of the uterine horn and cervix to PGE₂ and histamine. The mRNA expression of Otr and Ptger4 was inversely correlated with the mRNA expression of ll1b, ll6 in the uterine horn of Cmu-inoculated mice (P < 0.01 to P < 0.001), suggesting that the changes in the Otr and Ptger4mRNA expression might be linked to the changes in inflammatory cytokines. Lastly, this study also showed a novel physiological finding of the differential response to PGE₂ in mouse uterine horn and cervix.]]> Wed 17 Nov 2021 15:27:35 AEDT ]]> 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:41157 Wed 15 Feb 2023 10:57:18 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33086 Wed 15 Dec 2021 16:08:07 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43214 Wed 14 Sep 2022 14:34:31 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49614 Wed 14 Jun 2023 16:04:06 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47176 Wed 14 Dec 2022 15:55:59 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22103 Campylobacter jejuni has a broad host range but is especially associated with birds, both domestic and wild. Earlier studies have indicated thrushes of the genus Turdus in Europe to be frequently colonized with C. jejuni, and predominately with host-associated specific genotypes. The European Blackbird Turdus merula, has a large distribution in Europe, including some oceanic islands, and was also introduced to Australia by European immigrants in the 1850s. Methods: The host specificity and temporal stability of European Blackbird C. jejuni was investigated with multilocus sequence typing in a set of isolates collected from Sweden, Australia, and The Azores. Results: Remarkably, we found that the Swedish, Australian, and Azorean isolates were genetically highly similar, despite extensive spatial and temporal isolation. This indicates adaptation, exquisite specificity, and stability in time for European Blackbirds, which is in sharp contrast with the high levels of recombination and mutation found in poultry-related C. jejuni genotypes. Conclusion: The maintenance of host-specific signals in spatially and temporally separated C. jejuni populations suggests the existence of strong purifying selection for this bacterium in European Blackbirds.]]> Wed 11 Apr 2018 16:16:23 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22005 haemophilus influenzae and pharmacological inhibition in mouse and human macrophages augments phagocytosis, the production of reactive oxygen species, and microbicidal activity. Moreover, inhibition of miR-328 in respiratory models of infection, steroid-induced immunosuppression, and smoke-induced emphysema enhances bacterial clearance. Thus, miRNA pathways can be targeted in the lung to enhance host defence against a clinically relevant microbial infection and offer a potential new anti-microbial approach for the treatment of respiratory diseases.]]> Wed 11 Apr 2018 16:14:13 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14161 Wed 11 Apr 2018 16:03:17 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25052 Bacteroidales family S24-7 is a prominent example of one of these groups. Marker gene surveys indicate that members of this family are highly localized to the gastrointestinal tracts of homeothermic animals and are increasingly being recognized as a numerically predominant member of the gut microbiota; however, little is known about the nature of their interactions with the host. Results: Here, we provide the first whole genome exploration of this family, for which we propose the name "Candidatus Homeothermaceae," using 30 population genomes extracted from fecal samples of four different animal hosts: human, mouse, koala, and guinea pig. We infer the core metabolism of "Ca. Homeothermaceae" to be that of fermentative or nanaerobic bacteria, resembling that of related Bacteroidales families. In addition, we describe three trophic guilds within the family, plant glycan (hemicellulose and pectin), host glycan, and a-glucan, each broadly defined by increased abundance of enzymes involved in the degradation of particular carbohydrates. Conclusions: "Ca. Homeothermaceae" representatives constitute a substantial component of the murine gut microbiota, as well as being present within the human gut, and this study provides important first insights into the nature of their residency. The presence of trophic guilds within the family indicates the potential for niche partitioning and specific roles for each guild in gut health and dysbiosis.]]> Wed 11 Apr 2018 15:06:09 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30281 Fbln1c protected against CS-induced airway fibrosis and emphysema-like alveolar enlargement. In experimental COPD, this occurred through disrupted collagen organization and interactions with fibronectin, periostin, and tenascin-c. Genetic inhibition of Fbln1c also reduced levels of pulmonary inflammatory cells and proinflammatory cytokines/chemokines (TNF-a, IL-33, and CXCL1) in experimental COPD. Fbln1c⌿ mice also had reduced airway remodeling in experimental chronic asthma and pulmonary fibrosis. Our data show that Fbln1c may be a therapeutic target in chronic respiratory diseases.]]> Wed 11 Apr 2018 13:33:47 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:9558 Wed 11 Apr 2018 12:40:26 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:15132 Wed 11 Apr 2018 12:40:17 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:15695 Wed 11 Apr 2018 12:28:11 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30208 Wed 11 Apr 2018 11:33:34 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14158 Wed 11 Apr 2018 10:28:43 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31235 HI monocytes/macrophages and neutrophils. Body weight and clinical scores were recorded throughout the experiment. Results: We demonstrate that KB treatment attenuated cigarette smoke-induced lung inflammation as shown by reductions in levels of BAL IFNγ, CXCL9, CXCL10, CCL5, IL-6, G-CSF, and IL-17. KB additionally attenuated the quantity of BAL lymphocytes and macrophages. In parallel to the attenuation of lung inflammation, KB induced a systemic immune activation with increases in Ly6C^HI monocytes/macrophages and neutrophils. Conclusions: This is the first demonstration that subcutaneous administration of a microbial-based immunotherapy can attenuate cigarette smoke-induced lung inflammation, and modulate BAL lymphocyte and macrophage levels, while inducing a systemic immune activation and mobilization. These data provide a foundation for future studies exploring how KB may be used to either reverse or prevent progression of established emphysema and small airways disease associated with chronic cigarette smoke exposure. The data suggest the intriguing possibility that KB, which stimulates rather than suppresses systemic immune responses, might be a novel means by which the course of COPD pathogenesis may be altered.]]> Wed 10 Nov 2021 15:05:01 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40215 Wed 06 Jul 2022 16:26:34 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21107 Wed 04 Sep 2019 10:31:12 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34679 Trichinella spiralis-infected mice. In contrast, the constitutive HP⁺ MCs in the tongues of mMCP-5-null mice were poorly granulated and lacked mMC-CPA protein. Bone marrow-derived MCs were readily developed from the transgenic mice using IL-3. Although these MCs contained high levels of mMC-CPA mRNA, they also lacked the latter exopeptidase. mMCP-5 protein is therefore needed to target translated mMC-CPA to the secretory granule along with HP-containing serglycin proteoglycans. Alternately, mMCP-5 is needed to protect mMC-CPA from autolysis in the cell's granules. Fibronectin was identified as a target of mMCP-5, and the exocytosis ofmMCP-5from theMCs in the mouse's peritoneal cavity resulted in the expression of metalloproteinase protease-9, which has been implicated in arthritis. In support of the latter finding, experimental arthritis was markedly reduced in mMCP-5-null mice relative to wildtype mice in two disease models.]]> Wed 04 Sep 2019 09:38:57 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38106 Wed 04 Aug 2021 09:52:31 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49760 Tue 30 May 2023 18:39:10 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36521 Tue 26 May 2020 10:11:49 AEST ]]> 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:43418 Tue 20 Sep 2022 08:26:35 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54347 Tue 20 Feb 2024 16:20:08 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46351 n = 115) and Perth (n = 30), Australia. The Newcastle cohort was enriched with people with asthma (n = 37) and COPD (n = 38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC. Results: Increased gene expression of ACE2 was associated with older age (P = 0.03) and male sex (P = 0.03), but not with pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma patients (P = 0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in patients with asthma (P = 0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface, was increased (P = 0.02). ACE2 protein expression was also reduced in endobronchial biopsies from asthma patients. Conclusion: Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications.]]> Tue 15 Nov 2022 15:15:58 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41168 Tue 15 Aug 2023 14:44:00 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48325 Tue 14 Mar 2023 16:33:43 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47013 Tue 13 Dec 2022 11:48:24 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:15242 Tue 11 Jun 2019 11:55:23 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31941 Tue 10 Apr 2018 11:22:18 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39910 Thu 30 Jun 2022 12:44:37 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36424 61% or >162x10⁴ cells per mL sputum neutrophils) were randomised to receive either azithromycin or placebo for 12 weeks. Sputum and blood were obtained before and after 12 weeks of treatment. Gene expression was defined using microarrays. Networks were analysed using the Search Tool for the Retrieval of Interacting Gene database. In sputum, 403 genes were differentially expressed following azithromycin treatment (171 downregulated and 232 upregulated), and three following placebo treatment (one downregulated and two upregulated) compared to baseline (adjusted p<0.05 by paired t-test, fold-change >1.5). In blood, 138 genes were differentially expressed with azithromycin (121 downregulated and 17 upregulated), and zero with placebo compared to baseline (adjusted p<0.05 by paired t-test, fold-change >1.3). Network analysis revealed one key network in both sputum (14 genes) and blood (46 genes), involving interferon-stimulated genes, human leukocyte antigens and genes regulating T-cell responses. Long-term, low-dose azithromycin is associated with downregulation of genes regulating antigen presentation, interferon and T-cell responses, and numerous inflammatory pathways in the airways and blood of neutrophilic COPD patients.]]> Thu 30 Apr 2020 12:50:04 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23093 Thu 28 Oct 2021 13:04:03 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30656 Thu 28 Oct 2021 13:03:36 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32030 Thu 28 Oct 2021 13:03:16 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33793 –/–) mice had reduced mucin (MUC) 5 AC levels, but not MUC5B levels, in the airways as compared with wild‐type (WT) mice. Fbln1c interacted with fibronectin and periostin that was linked to collagen deposition around the small airways. Fbln1c^–/– mice with AAD also had reduced numbers of α‐smooth muscle actin‐positive cells around the airways and reduced airway contractility as compared with WT mice. After HDM challenge, these mice also had fewer airway inflammatory cells, reduced interleukin (IL)‐5, IL‐13, IL‐33, tumour necrosis factor (TNF) and CXCL1 levels in the lungs, and reduced IL‐5, IL‐33 and TNF levels in lung‐draining lymph nodes. Therapeutic targeting of Fbln1c reduced the numbers of GATA3‐positive Th2 cells in the lymph nodes and lungs after chronic HDM challenge. Treatment also reduced the secretion of IL‐5 and IL‐13 from co‐cultured dendritic cells and T cells restimulated with HDM extract. Human epithelial cells cultured with Fbln1c peptide produced more CXCL1 mRNA than medium‐treated controls. Our data show that Fbln1c may be a therapeutic target in chronic asthma.]]> Thu 28 Oct 2021 13:02:39 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:29749 Haemophilus influenzae is a host adapted human mucosal pathogen involved in a variety of acute and chronic respiratory tract infections, including chronic obstructive pulmonary disease and asthma, all of which rely on its ability to efficiently establish continuing interactions with the host. Here we report the characterization of a novel molybdenum enzyme, TorZ/MtsZ that supports interactions of H. influenzae with host cells during growth in oxygen-limited environments. Strains lacking TorZ/MtsZ showed a reduced ability to survive in contact with epithelial cells as shown by immunofluorescence microscopy and adherence/invasion assays. This included a reduction in the ability of the strain to invade human epithelial cells, a trait that could be linked to the persistence of H. influenzae. The observation that in a murine model of H. influenzae infection, strains lacking TorZ/MtsZ were almost undetectable after 72 h of infection, while ∼3.6 × 10³ CFU/mL of the wild type strain were measured under the same conditions is consistent with this view. To understand how TorZ/MtsZ mediates this effect we purified and characterized the enzyme, and were able to show that it is an S- and N-oxide reductase with a stereospecificity for S-sulfoxides. The enzyme converts two physiologically relevant sulfoxides, biotin sulfoxide and methionine sulfoxide (MetSO), with the kinetic parameters suggesting that MetSO is the natural substrate of this enzyme. TorZ/MtsZ was unable to repair sulfoxides in oxidized Calmodulin, suggesting that a role in cell metabolism/energy generation and not protein repair is the key function of this enzyme. Phylogenetic analyses showed that H. influenzae TorZ/MtsZ is only distantly related to the Escherichia coli TorZ TMAO reductase, but instead is a representative of a new, previously uncharacterized clade of molybdenum enzyme that is widely distributed within the Pasteurellaceae family of pathogenic bacteria. It is likely that MtsZ/TorZ has a similar role in supporting host/pathogen interactions in other members of the Pasteurellaceae, which includes both human and animal pathogens.]]> Thu 28 Oct 2021 12:36:21 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40658 Thu 28 Jul 2022 12:42:40 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41194 Thu 28 Jul 2022 11:12:36 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41158 Thu 28 Jul 2022 09:27:19 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45028 Zfp36 gene is an anti‐inflammatory protein that induces mRNA decay, especially of transcripts encoding inflammatory cytokines, including those implicated in COPD. Methods: Here, we identify a novel protective role for TTP in CS‐induced experimental COPD using Zfp36^aa/aa mice, a genetically modified mouse strain in which endogenous TTP cannot be phosphorylated, rendering it constitutively active as an mRNA‐destabilising factor. TTP wild‐type (Zfp36^+/+) and Zfp36^aa/aa active C57BL/6J mice were exposed to CS for four days or eight weeks, and the impact on acute inflammatory responses or chronic features of COPD, respectively, was assessed. Results: After four days of CS exposure, Zfp36^aa/aa mice had reduced numbers of airway neutrophils and lymphocytes and mRNA expression levels of cytokines compared to wild‐type controls. After eight weeks, Zfp36^aa/aa mice had reduced pulmonary inflammation, airway remodelling and emphysema‐like alveolar enlargement, and lung function was improved. We then used pharmacological treatments in vivo (protein phosphatase 2A activator, AAL_(S), and the proteasome inhibitor, bortezomib) to promote the activation and stabilisation of TTP and show that hallmark features of CS‐induced experimental COPD were ameliorated. Conclusion: Collectively, our study provides the first evidence for the therapeutic potential of inducing TTP as a treatment for COPD.]]> Thu 27 Oct 2022 09:28:02 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48574 Thu 24 Aug 2023 15:19:53 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33589 Thu 22 Nov 2018 13:41:25 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38252 Thu 19 Aug 2021 11:04:32 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38949 Thu 17 Mar 2022 08:49:09 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47210 Thu 15 Dec 2022 17:18:38 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36636 Thu 09 Dec 2021 11:03:23 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33310 Thu 09 Dec 2021 11:02:14 AEDT ]]> 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:31553 Sat 24 Mar 2018 08:44:25 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:8182 Sat 24 Mar 2018 08:36:15 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:1210 TCI). Following in vitro re-stimulation of lung-draining lymph node cells with MOMP; IFNγ mRNA increased 20-fold in cells from IN immunized animals (compared to non-immunized controls) while IFNγ levels increased 6- to 7-fold in TCI animals. Ten days post challenge non-immunized animals had >7000 IFU in their lungs, IN immunized animals <50 IFU and TCI immunized animals <1500 IFU. Thus, both intranasal and transcutaneous immunization protected mice against respiratory challenge with Chlamydia. The best protection was obtained following IN immunization and correlated with IFNγ production by mononuclear cells in lung-draining LN and MOMP-specific IgA in BAL.]]> Sat 24 Mar 2018 08:28:39 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:12415 + lymphocytes (Th2 cells) and their cytokines predominate in mild to moderate allergic asthma, whereas severe steroid-resistant asthma has more of a mixed Th2/Th1 phenotype with a Th17 component. Other immune cells, particularly neutrophils, macrophages and dendritic cells, as well structural cells such as epithelial and airway smooth muscle cells also produce disease-associated cytokines in asthma. Increased levels of these immune cells and cytokines have been identified in clinical samples and their potential role in disease demonstrated in studies using mouse models of asthma. Clinical trials with inhibitors of cytokines such as interleukin (IL)-4, -5 and tumour necrosis factor-α have had success in some studies but not others. This may reflect the design of the clinical trials, including treatments regimes and the patient population included in these studies. IL-13, -9 and granulocyte-macrophage colony-stimulating factor are currently being evaluated in clinical trials or preclinically and the outcome of these studies is eagerly awaited. Roles for IL-25, -33, thymic stromal lymphopoietin, interferon-γ, IL-17 and -27 in the regulation of asthma are just emerging, identifying new ways to treat inflammation. Careful interpretation of results from mouse studies will inform the development and application of therapeutic approaches for asthma. The most effective approaches may be combination therapies that suppress multiple cytokines and a range of redundant and disconnected pathways that separately contribute to asthma pathogenesis. Astute application of these approaches may eventually lead to the development of effective asthma therapeutics. Here we review the current state of knowledge in the field.]]> Sat 24 Mar 2018 08:14:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:12329 Sat 24 Mar 2018 08:11:37 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:11164 Sat 24 Mar 2018 08:08:30 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17439 Sat 24 Mar 2018 08:01:35 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21800 Haemophilus influenzae is one of the most commonly isolated bacteria. The relationship between chronic airway colonisation and the development of steroid-resistant neutrophilic asthma is unclear. Objectives: To investigate the relationship between H influenzae respiratory infection and neutrophilic asthma using mouse models of infection and ovalbumin (OVA)-induced allergic airways disease. Methods: BALB/c mice were intratracheally infected with H influenzae (day 10), intraperitoneally sensitised (day 0) and intranasally challenged (day 12–15) with OVA. Treatment groups were administered dexamethasone intranasally during OVA challenge. Infection, allergic airways disease, steroid sensitivity and immune responses were assessed (days 11, 16 and 21). Results: The combination of H influenzae infection and allergic airways disease resulted in chronic lung infection that was detected on days 11, 16 and 21 (21, 26 and 31 days after infection). Neutrophilic allergic airways disease and T helper 17 cell development were induced, which did not require active infection. Importantly, all features of neutrophilic allergic airways disease were steroid resistant. Toll-like receptor 4 expression and activation of phagocytes was reduced, but most significantly the influx and/or development of phagocytosing neutrophils and macrophages into the airways was inhibited. Conclusions: The combination of infection and allergic airways disease promotes bacterial persistence, leading to the development of a phenotype similar to steroid-resistant neutrophilic asthma and which may result from dysfunction in innate immune cells. This indicates that targeting bacterial infection in steroid-resistant asthma may have therapeutic benefit.]]> Sat 24 Mar 2018 07:59:21 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:20869 Sat 24 Mar 2018 07:57:58 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19841 Sat 24 Mar 2018 07:57:07 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20982 Sat 24 Mar 2018 07:54:20 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:5135 Sat 24 Mar 2018 07:49:39 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22006 100/FVC. Total lung capacity was increased in HE+DR males. HE males had elevated responses to methacholine. Neonatal hyperoxia alters lung function at mid-adulthood, especially in males.]]> Sat 24 Mar 2018 07:15:55 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:22016 Sat 24 Mar 2018 07:15:45 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22118 Sat 24 Mar 2018 07:13:18 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22106 Streptococcus pneumoniae induces Tregs that have potential to be harnessed therapeutically for asthma. In this study, mouse models of AAD were used to identify the S. pneumoniae components that have suppressive properties, and the mechanisms underlying suppression were investigated. We tested the suppressive capacity of type-3-polysaccharide (T3P), isolated cell walls, pneumolysoid (Ply) and CpG. When coadministered, T3P + Ply suppressed the development of: eosinophilic inflammation, Th2 cytokine release, mucus hypersecretion, and AHR. Importantly, T3P + Ply also attenuated features of AAD when administered during established disease. We show that NKT cells contributed to the development of AAD and also were suppressed by T3P + Ply treatment. Furthermore, adoptive transfer of NKT cells induced AHR, which also could be reversed by T3P + Ply. T3P + Ply-induced Tregs were essential for the suppression of NKT cells and AAD, which was demonstrated by Treg depletion. Collectively, our results show that the S. pneumoniae components T3P + Ply suppress AAD through the induction of Tregs that blocked the activity of NKT cells. These data suggest that S. pneumoniae components may have potential as a therapeutic strategy for the suppression of allergic asthma through the induction of Tregs and suppression of NKT cells.]]> Sat 24 Mar 2018 07:10:19 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38383 Mon 29 Jan 2024 17:45:07 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49577 Mon 22 May 2023 10:51:01 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35650 Mon 13 Nov 2023 11:04:35 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:50075 Fri 30 Jun 2023 12:02:10 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48427 Fri 26 Apr 2024 13:31:04 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53870 Fri 19 Jan 2024 12:39:17 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:55346 Fri 17 May 2024 15:50:21 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:35944 2+), phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2) and cyclic adenosine monophosphate (cAMP) were measured. R/S-4CMTB is a functionally selective ago-allosteric ligand that enhances Ca²⁺ response to acetate. Both R/S-4CMTB and S-4CMTB are more potent activators of pERK1/2 and inhibitors of forskolin-induced cAMP than acetate. S-4CMTB increased neutrophil infiltration in intestinal ischemia reperfusion injury (IRI). 2CTAP inhibited constitutive Ca²⁺ levels, antagonised acetate-induced pERK1/2 and prevented damage following IRI. This study characterises enantiomers of functionally selective ligands for FFA2 in cells stably expressing hFFA2. It highlights the novel roles of selective FFA2 enantiomers 4CMTB and 2CTAP on Ca²⁺, pERK1/2 and cAMP and their roles as allosteric modulators which, may assist in efforts to design novel therapeutic agents for FFA2-driven inflammatory diseases.]]> Fri 17 Jan 2020 15:33:08 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40169 in vitro model of the pulmonary epithelial-endothelial barrier and novel murine models to investigate the role of glycemic variability in influenza severity. In vitro, a history of glycemic variability significantly increased influenza-driven cell death and destruction of the epithelial-endothelial barrier. In vivo, influenza virus-infected mice with a history of glycemic variability lost significantly more body weight than mice with constant blood glucose levels. This increased disease severity was associated with markers of oxidative stress and hyperinflammation both in vitr and in vivo. Together, these results provide the first indication that glycemic variability may help drive the increased risk of severe influenza in people with diabetes mellitus.]]> Fri 15 Jul 2022 10:39:14 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38589 Fri 12 Nov 2021 15:59:30 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49363 Fri 12 May 2023 12:42:28 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38952 Haemophilus influenzae (NTHi), using immunofluorescence microscopy. In addition, expression of a known receptor of NTHi, platelet-activating factor receptor (PAFR), and two pro-inflammatory cytokines, interleukin 6 (IL-6) and interleukin-8 (IL-8), were determined using quantitative polymerase chain reaction. We observed a dose-dependent increase in NTHi adhesion to human bronchial epithelial cells following exposure to cow dung but not wood smoke extracts. Pre-treatment with PAFR antagonists, WEB-2086 and its analogue, C17, decreased adherence by NTHi to airway epithelial cells exposed to cow dung smoke. Both cow dung and wood smoke-induced expression of PAFR, as well as of IL-6 and IL-8, which was inhibited by WEB-2086 and C17. In conclusion, biomass smoke from combustion of cow dung and wood-induced expression of PAFR and airway inflammatory markers in human bronchial epithelial cells. Cow dung exposure, but not wood smoke exposure, mediated a measurable increase in NTHi adhesion to airway epithelial cells that was inhibited by PAFR antagonists. This work highlights the potential of PAFR as a therapeutic target for reducing the impact of hazardous biomass smoke exposure on respiratory health.]]> Fri 11 Mar 2022 14:48:35 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53577 Fri 08 Dec 2023 15:38:57 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:55056 Fri 05 Apr 2024 14:28:53 AEDT ]]>