Budesonide prevents but does not reverse sustained airway hyperresponsiveness in mice

Southam, David S.; Ellis, Russ; Wattie, Jennifer; Young, Simon S.; Inman, Mark D.

doi:10.1183/09031936.00125307

Cited by 12 publications

(9 citation statements)

References 45 publications

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“…Shifts in cell type such as the reduction in the relative number of macrophages or suppression of specific cytokines such as IFN-γ might explain these observations. The above described results are in accordance with other studies in which beneficial bacteria and budesonide have been individually investigated [1,13,23,24,51-53]. Additionally, B. breve , L. rhamnosus and budesonide treatments reduced the inflammation score and decreased the number of collagenous connective tissue fibers and proliferating cells in ovalbumin-sensitised and challenged mice as compared to the OVA/OVA-PBS group.…”

Section: Discussionsupporting

confidence: 91%

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Bifidobacterium breve and Lactobacillus rhamnosus treatment is as effective as budesonide at reducing inflammation in a murine model for chronic asthma

Sagar¹,

Morgan²,

Chen³

et al. 2014

Respir Res

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BackgroundAsthma is estimated to affect as many as 300 million people worldwide and its incidence and prevalence are rapidly increasing throughout the world, especially in children and within developing countries. Recently, there has been a growing interest in the use of potentially beneficial bacteria for allergic diseases. This study is aimed at exploring the therapeutic effects of long-term treatment with two different beneficial bacterial strains (Bifidobacterium breve M-16 V and Lactobacillus rhamnosus NutRes1) and a glucocorticoid (budesonide), as a reference treatment, on inflammatory response in a murine model for chronic allergic asthma.MethodsTo mimic the chronic disease in asthmatic patients, we used the murine ovalbumin-induced asthma model combined with prolonged allergen exposure. Airway function; pulmonary airway inflammation; airway remodelling, mRNA expression of pattern recognition receptors, Th-specific cytokines and transcription factors in lung tissue; mast cell degranulation; in vitro T cell activation; and expression of Foxp3 in blood Th cells were examined.ResultsLactobacillus rhamnosus reduced lung resistance to a similar extent as budesonide treatment in chronically asthmatic mice. Pulmonary airway inflammation, mast cell degranulation, T cell activation and airway remodelling were suppressed by all treatments. Beneficial bacteria and budesonide differentially modulated the expression of toll-like receptors (TLRs), nod-like receptors (NLRs), cytokines and T cell transcription factors. Bifidobacterium breve induced regulatory T cell responses in the airways by increasing Il10 and Foxp3 transcription in lung tissue as well as systemic by augmenting the mean fluorescence intensity of Foxp3 in blood CD4+ T cells.ConclusionThese findings show that Bifidobacterium breve M-16 V and Lactobacillus rhamnosus NutRes1 have strong anti-inflammatory properties that are comparable to budesonide and therefore may be beneficial in the treatment of chronic asthma.

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Section: Discussionsupporting

confidence: 91%

“…Besides the undesirable side effects of long-term GC therapy, a significant number of asthmatics is steroid resistant and fails to respond to this therapy [13,14]. These limitations of GCs therapy highlight the need for novel therapeutics with long-term benefits, greater disease control and increased efficacy.…”

Section: Introductionmentioning

confidence: 99%

Bifidobacterium breve and Lactobacillus rhamnosus treatment is as effective as budesonide at reducing inflammation in a murine model for chronic asthma

Sagar¹,

Morgan²,

Chen³

et al. 2014

Respir Res

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show abstract

“…Similar observations were reported in a chronic OVA-induced asthma model when budesonide was given for four weeks following allergen cessation, however in this case no differences in collagen deposition and smooth muscle mass were observed [2]. Similar results have been obtained following the co-application of OVA and dexamethasone, which reduced goblet cells hyperplasia but did not affect smooth muscle thickness [41], [42].…”

Section: Discussionsupporting

confidence: 86%

Compartmental and Temporal Dynamics of Chronic Inflammation and Airway Remodelling in a Chronic Asthma Mouse Model

et al. 2014

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BackgroundAllergic asthma is associated with chronic airway inflammation and progressive airway remodelling. However, the dynamics of the development of these features and their spontaneous and pharmacological reversibility are still poorly understood. We have therefore investigated the dynamics of airway remodelling and repair in an experimental asthma model and studied how pharmacological intervention affects these processes.MethodsUsing BALB/c mice, the kinetics of chronic asthma progression and resolution were characterised in absence and presence of inhaled corticosteroid (ICS) treatment. Airway inflammation and remodelling was assessed by the analysis of bronchoalveolar and peribronichal inflammatory cell infiltrate, goblet cell hyperplasia, collagen deposition and smooth muscle thickening.ResultsChronic allergen exposure resulted in early (goblet cell hyperplasia) and late remodelling (collagen deposition and smooth muscle thickening). After four weeks of allergen cessation eosinophilic inflammation, goblet cell hyperplasia and collagen deposition were resolved, full resolution of lymphocyte inflammation and smooth muscle thickening was only observed after eight weeks. ICS therapy when started before the full establishment of chronic asthma reduced the development of lung inflammation, decreased goblet cell hyperplasia and collagen deposition, but did not affect smooth muscle thickening. These effects of ICS on airway remodelling were maintained for a further four weeks even when therapy was discontinued.ConclusionsUtilising a chronic model of experimental asthma we have shown that repeated allergen exposure induces reversible airway remodelling and inflammation in mice. Therapeutic intervention with ICS was partially effective in inhibiting the transition from acute to chronic asthma by reducing airway inflammation and remodelling but was ineffective in preventing smooth muscle hypertrophy.

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“…Twenty-five microliters of budesonide solution, corresponding to 1 or 3 mg/kg body weight, was administered via an intranasal route to each mouse for 3 days followed by LPS exposure at 1 h after last budesonide treatment [18]. …”

Section: Methodsmentioning

confidence: 99%

Nrf2 deficiency influences susceptibility to steroid resistance via HDAC2 reduction

Adenuga

Caito

Yao

et al. 2010

Biochemical and Biophysical Research Communications

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Abnormal lung inflammation and oxidant burden are associated with a significant reduction in histone deacetylase 2 (HDAC2) abundance and steroid resistance. We hypothesized that Nrf2 regulates steroid sensitivity via HDAC2 in response to inflammation in mouse lung. Furthermore, HDAC2 deficiency leads to steroid resistance in attenuating lung inflammatory response, which may be due to oxidant/antioxidant imbalance. Loss of antioxidant transcription factor Nrf2 resulted in decreased HDAC2 in lung, and increased inflammatory lung response which was not reversed by steroid. Thus, steroid resistance or inability of steroids to control lung inflammatory response is dependent on Nrf2-HDAC2 axis. These findings have implications in steroid resistance, particularly during the conditions of oxidative stress when the lungs are more susceptible to inflammatory response, which is seen in patients with chronic obstructive pulmonary disease, asthma, rheumatoid arthritis, and inflammatory bowel disease.

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Budesonide prevents but does not reverse sustained airway hyperresponsiveness in mice

Cited by 12 publications

References 45 publications

Bifidobacterium breve and Lactobacillus rhamnosus treatment is as effective as budesonide at reducing inflammation in a murine model for chronic asthma

Bifidobacterium breve and Lactobacillus rhamnosus treatment is as effective as budesonide at reducing inflammation in a murine model for chronic asthma

Compartmental and Temporal Dynamics of Chronic Inflammation and Airway Remodelling in a Chronic Asthma Mouse Model

Nrf2 deficiency influences susceptibility to steroid resistance via HDAC2 reduction

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