https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47161 Cissampelos sympodialis Eichler, Menispermaceae, is a native Brazilian plant used in folk medicine to treat asthma and has central nervous system effects. Anxiety is a prevalent comorbidity of asthma raising the potential for the development of monotherapy for both diseases. We evaluated the effectiveness of the alcoholic fraction of leaves of C. sympodialis and its isolated alkaloid warifteine in treating anxiety- and asthma-like symptoms in mice with ovalbumin-induced allergic airway disease. Ovalbumin-sensitized BALB/c mice were treated with the plant extract or alkaloid orally, or with diazepam or dexamethasone controls, before ovalbumin challenge. Plant extract and warifteine treatments ameliorated anxiety-like symptoms and improved respiratory rate similar to diazepam in conscious allergic mice but did not ameliorate airway hyper-responsiveness. Plant extract and warifteine also reduced leukocyte migration into the airways and Th2 cytokine levels in bronchoalveolar lavage and lung tissue similar to dexamethasone. Our data indicate that C. sympodialis and its isolated alkaloid warifteine represent potential monotherapies to treat anxiety and asthma symptoms.]]> Wed 14 Dec 2022 15:41:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43823 Tue 04 Oct 2022 11:04:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33077 Chlamydia, Haemophilus influenzae, influenza, and respiratory syncytial virus respiratory tract infections and ovalbumin-induced, severe, steroid-insensitive allergic airway disease (SSIAAD) in BALB/c mice were developed and interrogated. Results: Infection induced increases in the levels of microRNA (miRNA)-21 (miR-21) expression in the lung during SSIAAD, whereas expression of the miR-21 target phosphatase and tensin homolog was reduced. This was associated with an increase in levels of phosphorylated Akt, an indicator of phosphoinositide 3-kinase (PI3K) activity, and decreased nuclear histone deacetylase (HDAC)2 levels. Treatment with an miR-21-specific antagomir (Ant-21) increased phosphatase and tensin homolog levels. Treatment with Ant-21, or the pan-PI3K inhibitor LY294002, reduced PI3K activity and restored HDAC2 levels. This led to suppression of airway hyperresponsiveness and restored steroid sensitivity to allergic airway disease. These observations were replicated with SSIAAD associated with 4 different pathogens. Conclusion: We identify a previously unrecognized role for an miR-21/PI3K/HDAC2 axis in SSIAAD. Our data highlight miR-21 as a novel therapeutic target for the treatment of this form of asthma.]]> Fri 24 Aug 2018 14:41:05 AEST ]]> https://nova.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 ]]>