https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38039 Wed 28 Jul 2021 09:42:45 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51026 Wed 28 Feb 2024 16:13:12 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50469 Wed 28 Feb 2024 15:49:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47737 Wed 25 Jan 2023 15:07:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11267 Wed 24 Jul 2013 22:28:44 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55346 Wed 22 May 2024 12:26:00 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49965 Wed 21 Jun 2023 11:57:33 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45438 Wed 20 Mar 2024 15:45:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:31003 Wed 19 Jan 2022 15:18:59 AEDT ]]> https://nova.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://nova.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://nova.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://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41157 Wed 15 Feb 2023 10:57:18 AEDT ]]> 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:47060 Wed 13 Mar 2024 08:04:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14161 Wed 11 Apr 2018 16:03:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14160 -/-), 4^-/- or 2/4^-/- BALB/c mice. Wt mice had moderate disease and infection. TLR2^-/- mice had more severe disease and more intense and prolonged infection compared to other groups. TLR4^-/- mice were asymptomatic. TLR2/4^-/- mice had severe early disease and persistent infection, which resolved thereafter consistent with the absence of symptoms in TLR4^-/- mice. Wt mice mounted robust innate and adaptive responses with an influx of natural killer (NK) cells, neutrophils, myeloid (mDCs) and plasmacytoid (pDCs) dendritic cells, and activated CD4⁺ and CD8⁺ T-cells into the lungs. Wt mice also had effective production of interferon (IFN)c in the lymph nodes and lung, and proliferation of lymph node T-cells. TLR2^-/- mice had more intense and persistent innate (particularly neutrophil) and adaptive cell responses and IL-17 expression in the lung, however IFNγ responses and T-cell proliferation were reduced. TLR2/4^-/- mice had reduced innate and adaptive responses. Most importantly, neutrophil phagocytosis was impaired in the absence of TLR2. Thus, TLR2 expression, particularly on neutrophils, is required for effective control of Chlamydia respiratory infection in early life. Loss of control of infection leads to enhanced but ineffective TLR4-mediated inflammatory responses that prolong disease symptoms. This indicates that TLR2 agonists may be beneficial in the treatment of early life Chlamydia infections and associated diseases.]]> Wed 11 Apr 2018 13:47:06 AEST ]]> https://nova.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://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14152 Wed 11 Apr 2018 12:41:22 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30208 Wed 11 Apr 2018 11:33:34 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14153 Wed 11 Apr 2018 10:56:29 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14158 Wed 11 Apr 2018 10:28:43 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41553 Wed 08 May 2024 09:45:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48779 Wed 05 Apr 2023 14:30:29 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52146 Wed 04 Oct 2023 10:20:41 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:31006 Wed 02 Mar 2022 14:28:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50715 Wed 02 Aug 2023 16:17:49 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49760 Tue 30 May 2023 18:39:10 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54542 Tue 27 Feb 2024 20:40:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48325 Tue 14 Mar 2023 16:33:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47013 Tue 13 Dec 2022 11:48:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47003 Tue 13 Dec 2022 10:59:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:31941 Tue 10 Apr 2018 11:22:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54158 Tue 06 Feb 2024 12:17:30 AEDT ]]> https://nova.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://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41158 Thu 28 Jul 2022 09:27:19 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45342 Thu 27 Oct 2022 15:17:41 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15996 Thu 18 Feb 2021 11:21:19 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47210 Thu 15 Dec 2022 17:18:38 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34597 Thu 13 Jan 2022 10:31:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50895 Thu 10 Aug 2023 10:29:50 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49088 Thu 04 May 2023 13:43:05 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33083 Thu 03 Feb 2022 12:19:51 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1878 Sat 24 Mar 2018 08:31:18 AEDT ]]> https://nova.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://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:11164 Sat 24 Mar 2018 08:08:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20869 Sat 24 Mar 2018 07:57:58 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16980 Sat 24 Mar 2018 07:55:27 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5109 Sat 24 Mar 2018 07:48:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5387 Sat 24 Mar 2018 07:43:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27093 Sat 24 Mar 2018 07:40:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22009 Chlamydia and Haemophilus lung infection-induced SSIAAD. We used these models to investigate the effects of clarithromycin and amoxicillin treatment on immune responses and airways hyper-responsiveness (AHR) in Ova-induced, T helper lymphocyte (Th) 2 -associated steroid-sensitive AAD and infection-induced Th1/Th17-associated SSIAAD compared with dexamethasone treatment. Results: Clarithromycin and amoxicillin had similar antimicrobial effects on infection. Amoxicillin did attenuate some features, but did not broadly suppress either form of AAD. It did restore steroid sensitivity in SSIAAD by reducing infection. In contrast, clarithromycin alone widely suppressed inflammation and AHR in both steroid-sensitive AAD and SSIAAD. This occurred through reductions in Th2 responses that drive steroid-sensitive eosinophilic AAD and tumour necrosis factor a and interleukin 17 responses that induce SSIAAD. Conclusions: Macrolides have broad anti-inflammatory effects in AAD that are likely independent of their antimicrobial effects. The specific responses that are suppressed are dependent upon the responses that dominate during AAD.]]> Sat 24 Mar 2018 07:15:55 AEDT ]]> https://nova.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://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22024 Sat 24 Mar 2018 07:15:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21997 Sat 24 Mar 2018 07:14:33 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 ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22114 Chlamydia-induced lung disease was observed 10–15 days after infection, as evidenced by increased bacterial numbers and histopathology in the lung and a reduction in weight gain. After 6 weeks, infection and histopathology had resolved and the rate of weight gain had recovered. Neonatal but not adult infection resulted in significant decreases in interleukin-5 production from helper T cells and by the numbers of eosinophils recruited to the lung in response to ovalbumin exposure. Remarkably, the effects of early-life infection were associated with the generation of both type 1 and 2 ovalbumin-specific helper T-cell cytokine and antibody responses. Furthermore, although neonatal infection significantly attenuated eosinophilia, the generation of the mixed T-cell response exacerbated other hallmark features of asthma: mucus hypersecretion and airway hyperresponsiveness. Moreover, infection prolonged the expression of AAD and these effects were restricted to early-life infection. Conclusions: Early-life chlamydial infection induces a mixed type 1 and 2 T-cell response to antigen, which differentially affects the development of key features of AAD in the adult.]]> Sat 24 Mar 2018 07:13:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22116 Streptococcus pneumoniae (Spn). The effect of Spn IMT on the development of asthma [allergic airways disease (AAD)] was determined in mice. Killed Spn was administered before, during or after ovalbumin sensitization, and the subsequent development of AAD was assessed. IMT attenuated T cell cytokine production, goblet cell hyperplasia, airways hyperresponsiveness (AHR), and eosinophil numbers in the blood, bronchoalveolar lavage fluid and peribronchial tissue. This indicates the potential of Spn as an IMT for asthma.]]> Sat 24 Mar 2018 07:13:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22105 Sat 24 Mar 2018 07:10:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22108 Sat 24 Mar 2018 07:10:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22126 Sat 24 Mar 2018 07:09:58 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38383 Mon 29 Jan 2024 17:45:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53947 Mon 22 Jan 2024 16:56:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42355 Mon 22 Aug 2022 14:01:30 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47389 Mon 16 Jan 2023 15:45:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46962 Il22^−/−) mice. CS-induced airway remodelling and emphysema-like alveolar enlargement did not occur in Il22^−/− mice. Il22^−/− mice had improved lung function in terms of airway resistance, total lung capacity, inspiratory capacity, forced vital capacity and compliance. These data highlight important roles for IL-22 and its receptors in human COPD and CS-induced experimental COPD.]]> Mon 12 Dec 2022 14:27:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54764 Mon 11 Mar 2024 15:00:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53538 Mon 04 Dec 2023 15:44:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22044 Chlamydia, Haemophilus influenzae and Streptococcus pneumoniae in early life may promote permanent deleterious changes in immunity, lung structure, and function that predispose to, or increase the severity of chronic respiratory diseases in later life. For example, these infections increase immune responses, which drive subsequent asthma pathogenesis. Targeting the pathways involved with specific inhibitors or agonists may prevent these consequences of early-life infection. Vaccination and immunomodulatory therapies that control the infections and their sequelae may also be efficacious.]]> Mon 01 Feb 2016 13:04:15 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36049 Fri 31 Jan 2020 13:13:08 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50075 Fri 30 Jun 2023 12:02:10 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42107 Fri 26 Aug 2022 11:23:51 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48427 Fri 26 Apr 2024 13:31:04 AEST ]]> 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 ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54960 Fri 22 Mar 2024 15:34:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47272 Fri 13 Jan 2023 10:17:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49107 Fri 05 May 2023 11:32:08 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55056 Fri 05 Apr 2024 14:28:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39978 Fri 01 Jul 2022 09:58:32 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33085 -/-) and TLR4-deficient (Tlr4^-/-) mice. CS-induced airway fibrosis, characterized by increased collagen deposition around small airways, was not altered in Tlr2^-/- mice but was attenuated in Tlr4^-/- mice compared with CS-exposed WT controls. However, Tlr2^-/- mice had increased CS-induced emphysema-like alveolar enlargement, apoptosis, and impaired lung function, while these features were reduced in Tlr4^-/- mice compared with CS-exposed WT controls. Taken together, these data highlight the complex roles of TLRs in the pathogenesis of COPD and suggest that activation of TLR2 and/or inhibition of TLR4 may be novel therapeutic strategies for the treatment of COPD.]]> Fri 01 Apr 2022 09:24:33 AEDT ]]>