https://ogma.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31003 Wed 19 Jan 2022 15:18:59 AEDT ]]> 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:39240 h2 signalling, improved their outcomes. Methods: Male BALB/c mice were intranasally sensitized with house dust mite antigen (Der p 1) for 2 weeks; the mice were then inoculated intranasally with a single dose of pandemic H1N1 (pH1N1). The mice were administered intraperitoneally anti-IL-4Rα through either a prophylactic or a therapeutic treatment strategy. Results: Infection with pH1N1 of mice sensitized to house dust mite (HDM) led to a 24% loss in weight by day 7 of infection (versus 14% in non-sensitized mice; p < .05). This was accompanied by increased viral load in the airways and a dampened anti-viral host responses to the infection. Treatment of HDM sensitized mice with a monoclonal antibody against IL-4Rα prior to or following pH1N1 infection prevented the excess weight loss, reduced the viral load in the lungs and ameliorated airway eosinophilia and systemic inflammation related to the pH1N1 infection. Conclusion: Together, these data implicate allergic asthma as a significant risk factor for H1N1-related morbidity and reveal a potential therapeutic role for IL-4Rα signalling blockade in reducing the severity of influenza infection in those with allergic airway disease.]]> Wed 10 Aug 2022 08:53:16 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30800 Wed 02 Mar 2022 14:24:09 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:33083 Thu 03 Feb 2022 12:19:51 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:14651 Sat 24 Mar 2018 08:20:46 AEDT ]]> https://ogma.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://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19679 Sat 24 Mar 2018 07:53:38 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27531 Sat 24 Mar 2018 07:28:58 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:33076 Chlamydia and Haemophilus respiratory infection-mediated, ovalbumin-induced severe, steroid-resistant allergic airway disease. These models share the hallmark features of human disease, including elevated airway neutrophils, and NLRP3 inflammasome and IL-1ß responses. The roles and potential for targeting of NLRP3 inflammasome, caspase-1, and IL-1ß responses in experimental severe, steroid-resistant asthma were examined using a highly selective NLRP3 inhibitor, MCC950; the specific caspase-1 inhibitor Ac-YVAD-cho; and neutralizing anti-IL-1ß antibody. Roles for IL-1ß-induced neutrophilic inflammation were examined using IL-1ß and anti-Ly6G. Measurements and Main Results: Chlamydia and Haemophilus infections increase NLRP3, caspase-1, IL-1ß responses that drive steroid-resistant neutrophilic inflammation and airway hyperresponsiveness. Neutrophilic airway inflammation, disease severity, and steroid resistance in human asthma correlate with NLRP3 and IL-1ß expression. Treatment with anti-IL-1ß, Ac- YVAD-cho, and MCC950 suppressed IL-1ß responses and the important steroid-resistant features of disease in mice, whereas IL-1ß administration recapitulated these features. Neutrophil depletion suppressed IL-1ß-induced steroid-resistant airway hyperresponsiveness. Conclusions: NLRP3 inflammasome responses drive experimental severe, steroid-resistant asthma and are potential therapeutic targets in this disease.]]> Fri 24 Aug 2018 14:40:56 AEST ]]>