https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14610 Sat 24 Mar 2018 08:20:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20754 Sat 24 Mar 2018 08:00:25 AEDT ]]> https://nova.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://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19945 Sat 24 Mar 2018 07:58:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20625 Sat 24 Mar 2018 07:55:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21262 Sat 24 Mar 2018 07:54:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22280 in silico and confirmed in luciferase reporter assays. miR-9 function was inhibited with sequence-specific antagomirs. The efficacy of DEX was assessed by quantifying glucocorticoid receptor (GR) cellular localization, protein phosphatase 2A (PP2A) activity, and AHR. Results: Exposure of pulmonary macrophages to IFN-γ/LPS synergistically induced miR-9 expression; reduced levels of its target transcript, protein phosphatase 2 regulatory subunit B (B56) δ isoform; attenuated PP2A activity; and inhibited DEX-induced GR nuclear translocation. Inhibition of miR-9 increased both PP2A activity and GR nuclear translocation in macrophages and restored steroid sensitivity in multiple models of steroid-resistant AHR. Pharmacologic activation of PP2A restored DEX efficacy and inhibited AHR. MiR-9 expression was increased in sputum of patients with neutrophilic but not those with eosinophilic asthma. Conclusion: MiR-9 regulates GR signaling and steroid-resistant AHR. Targeting miR-9 function might be a novel approach for the treatment of steroid-resistant asthma.]]> Sat 24 Mar 2018 07:17:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22195 Sat 24 Mar 2018 07:16:25 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22049 Sat 24 Mar 2018 07:15:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22111 Ifn-ε–deficient mice had increased susceptibility to infection of the FRT by the common sexually transmitted infections (STIs) herpes simplex virus 2 and Chlamydia muridarum. Thus, IFN-ε is a potent antipathogen and immunoregulatory cytokine that may be important in combating STIs that represent a major global health and socioeconomic burden.]]> Sat 24 Mar 2018 07:13:18 AEDT ]]>