https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43499 Wed 21 Sep 2022 10:05:07 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15236 Wed 11 Apr 2018 17:06:49 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13805 Wed 11 Apr 2018 10:28:58 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21994 Thu 28 Oct 2021 12:36:38 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38615 Thu 25 Nov 2021 14:39:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30071 Thu 24 Mar 2022 11:36:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33082 (S)), or inhibiting proteasome activity with bortezomib (BORT), could suppress experimental AAD. Methods: Acute AAD was induced in C57BL/6 mice by intraperitoneal sensitization with ovalbumin (OVA) in combination with intranasal (i.n) exposure to OVA. Chronic AAD was induced in mice with prolonged i.n exposure to crude house dust mite (HDM) extract. Mice were treated with vehicle, FTY720, AAL_(S), BORT or AAL_(S)+- BORT and hallmark features of AAD assessed. Results: AAL_(S) reduced the severity of acute AAD by suppressing tissue eosinophils and inflammation, mucus-secreting cell (MSC) numbers, type 2-associated cytokines (interleukin (IL)-33, thymic stromal lymphopoietin, IL-5 and IL-13), serum immunoglobulin (Ig)E and airway hyper-responsiveness (AHR). FTY720 only suppressed tissue inflammation and IgE. BORT reduced bronchoalveolar lavage fluid (BALF) and tissue eosinophils and inflammation, IL-5, IL-13 and AHR. Combined treatment with AAL_(S)+BORT had complementary effects and suppressed BALF and tissue eosinophils and inflammation, MSC numbers, reduced the production of type 2 cytokines and AHR. AAL (S) , BORT and AAL (S) +BORT also reduced airway remodelling in chronic AAD. Conclusion: These findings highlight the potential of combination therapies that enhance PP2A and inhibit proteasome activity as novel therapeutic strategies for asthma.]]> Thu 17 Mar 2022 14:36:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21993 Thu 14 Apr 2022 11:02:37 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29496 Thu 14 Apr 2022 10:58:05 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:31198 Thu 13 Jan 2022 10:30:44 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:9455 Sat 24 Mar 2018 08:41:08 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7036 Sat 24 Mar 2018 08:37:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1890 Sat 24 Mar 2018 08:33:21 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13872 Sat 24 Mar 2018 08:25:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13898 Sat 24 Mar 2018 08:25:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14218 Sat 24 Mar 2018 08:24:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15982 -/- mice had reduced infection, inflammation, and mucus-secreting cell hyperplasia. Surprisingly, infection of wild-type (WT) mice did not increase IL-13 production but reduced IL-13Rα2 decoy receptor levels compared with sham-inoculated controls. Infection of WT but not Il13^-/- mice induced persistent AHR. Infection and associated pathology were restored in infected Il13^-/- mice by reconstitution with IL-13. Stat6^-/- mice were also largely protected. Neutralization of IL-13 during infection prevented subsequent infection-induced severe AAD. Thus, early-life Chlamydia respiratory infection reduces IL-13Rα2 production, which may enhance the effects of constitutive IL-13 and promote more severe infection, persistent AHR, and AAD.]]> Sat 24 Mar 2018 08:23:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14498 Sat 24 Mar 2018 08:21:40 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12772 Sat 24 Mar 2018 08:18:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13282 Sat 24 Mar 2018 08:15:15 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19563 Sat 24 Mar 2018 07:58:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20387 Sat 24 Mar 2018 07:58:09 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17901 Sat 24 Mar 2018 07:56:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22112 Chlamydia muridarum bacteria on glucocorticoid (GR) and mineralocorticoid (MR) receptors in the adult mouse hippocampus. In male adults infected at birth, circulating corticosterone was significantly increased when compared to same sex controls; while neonatal infection resulted in female adults with significantly increased GR mRNA compared to same sex controls. When comparing males and females after neonatal infection, males had significantly less GR protein than females. Interestingly, after control treatment, males had significantly more GR mRNA, MR mRNA, and GR protein with significantly lower corticosterone than females. Neonatal respiratory infection significantly impacts adult hippocampal GR and MR, and circulating corticosterone in a sex-specific manner potentially altering stress responsivity.]]> Sat 24 Mar 2018 07:13:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22117 + T-helper 2 lymphocyte-like (Th type-2) inflammatory responses in the lung. Although IL-25 up-regulates IL-13 in the lung, the contribution of this and other type 2 cytokine signalling pathways to the induction and persistence of airways hyper-reactivity (AHR) and allergic inflammation are unclear. Objective: To determine the downstream factors employed by IL-25 to induce Th type-2 pulmonary inflammation and AHR. Methods: IL-25 was delivered to the airways of BALB/c mice by intra-tracheal (i.t.) instillation and AHR and Th type-2 inflammatory responses were characterized in wild type (WT) and Th type-2-cytokine and -signalling pathway-deficient (−/−) mice. Results: IL-25 treatment resulted in AHR, eosinophilic inflammation, mucus hypersecretion and a progressive increase in the production of Th type-2 cytokines in the lungs. Levels of arginase-I (arg-I) and eotaxin were also elevated by IL-25 treatment. A significant reduction in AHR, and attenuation of mucus production was observed in IL-25-treated IL-13^−/−, IL-4 receptor alpha (IL-4Rα^−/−)- and signal-transducer-and-activator-of-transcription-factor-6 (STAT6^−/−)-deficient mice. AHR was also inhibited in IL-4^−/−- and IL-5/eotaxin(1)^−/−- deficient mice treated with IL-25, however, mucus hypersecretion was not completely ablated. IL-25 promoted Th type-2 responses by directly acting on naïve T cells. Conclusion: IL-25 potently (single dose) induces sustained AHR and acute pulmonary inflammation with eosinophilia. IL-25-induced AHR is dependent on the production of Th type-2 cytokines, and removal of IL-13 and its signal transduction pathway prevents IL-25-induced airways inflammation and AHR. IL-25 potently induces inflammatory cascades that may exacerbate allergic airways inflammation by promoting Th type-2 cytokine responses in conjunction with the up-regulation of factors (eotaxin and arg-I) that can amplify inflammation associated with allergic disorders. Dysregulation in IL-25 production may predispose to features of allergic airways disease.]]> Sat 24 Mar 2018 07:13:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22107 Sat 24 Mar 2018 07:10:20 AEDT ]]>