Model Of Chronic Asthma Research Articles

Bu-Shen-Yi-Qi formula ameliorates airway remodeling in murine chronic asthma by modulating airway inflammation and oxidative stress in the lung

Bu-Shen-Yi-Qi formula (BSYQF) could suppress chronic airway inflammation according to previous studies. However, there is relatively little direct experimental evidence to evaluate the effects of BSYQF treatment on airway remodeling in chronic asthma. Recent evidence suggests that oxidative stress is involved in airway inflammation and airway remodeling in chronic asthma. BSYQF which includes various of chemical components having antioxidant effects, could be beneficial in attenuating airway remodeling in chronic asthma. The purpose of this study was to elucidate the effect of BSYQF treatment on airway remodeling and investigate its potential mechanisms in chronic asthma. To develop the murine models of chronic asthma, BALB/c mice were sensitized and challenged to ovalbumin for 8 weeks. BSYQF (5, 10, 20 g raw herbs/kg body weight) or tiotropium bromide (0.1 mM) were administered orally and intranasal instillation, respectively. The effect of BSYQF on pulmonary inflammation and remodeling was evaluated. The parameters of oxidative stress in the lung were analyzed. BSYQF treatment reduced airway hyperresponsiveness (AHR), Th2 response including IL-4, IL-13, and OVA-specific IgE and IgG1, transforming growth factor-β (TGF-β), vascular endothelium growth factor (VEGF), airway inflammation and airway remodeling including smooth muscle thickening and peribronchial collagen deposition. As for oxidative stress, BSYQF treatment reduced reactive oxygen species (ROS), Malondialdehyde (MDA), NO, and the expression of inducible nitric oxide synthase (iNOS), but increased significantly glutathione (GSH) /Oxidized glutathione(GSSH) ratios in the lung, restored mitochondrial ultrastructural changes of bronchial epithelia and ATP levels in the lung.In summary, this study suggested that BSYQF treatment ameliorated airway remodeling and alleviated asthmatic features in chronic asthma models. Anti-inflammatory and antioxidant effect of BSYQF may explain why BSYQF has effects on preventing airway remodeling.

A specific combined long-chain polyunsaturated fatty acid supplementation reverses fatty acid profile alterations in a mouse model of chronic asthma

BackgroundThe immune-modulating potential of long-chain polyunsaturated fatty acids (LCPUFAs) based on their conversion into lipid mediators in inflammatory situations has been proven by several studies. Respecting the immune-modulative role of lipid mediators in bronchoconstriction, airway inflammation and resolution of inflammatory processes, LCPUFAs play an important role in asthma. To design a disease-specific and most beneficial LCPUFA supplementation strategy, it is essential to understand how asthma alters LCPUFA profiles. Therefore, this study characterizes the alterations of LCPUFA profiles induced by allergic asthma. In addition, this study explores whether a simple eicosapentaenoic acid (EPA) alone or a specific combined LCPUFA supplementation could restore imbalanced LCPUFA profiles.MethodsMice were sensitized with a daily dose of 40 μg house dust mite (HDM)-extract in a recall model and fed with either normal diet, EPA or a specific combined (sc)-LCPUFA supplementation containing EPA, docosahexaenoic acid (DHA), γ -linolenic acid (GLA) and stearidonic acid (SDA) for 24 days. After recall with HDM, mice were sacrificed and blood and lung tissue were collected. Fatty acid profiles were determined in plasma, blood cells and lung cells of asthmatic mice by capillary gas-chromatography.ResultsIn lung cells of asthmatic mice, arachidonic acid (AA, p < 0.001) and DHA (p < 0.01) were increased while dihomo-γ-linolenic acid (DGLA, p < 0.05) was decreased. EPA supplementation increased only EPA (p < 0.001) and docosapentaenoic acid (DPA, p < 0.001), but neither DGLA nor DHA in lung cells of asthmatic mice. In contrast, a specific combined dietary supplementation containing n-3 and n-6 LCPUFAs could decrease AA (p < 0.001), increase EPA (p < 0.001), DPA (p < 0.001) and DHA (p < 0.01) and could reverse the lack of DGLA (p < 0.05).ConclusionsIn summary, allergic asthma alters LCPUFA profiles in blood and lung tissue. In contrast to the EPA supplementation, the distinct combination of n-3 and n-6 LCPUFAs restored the LCPUFA profiles in lung tissue of asthmatic mice completely. Subsequently, sc-LCPUFA supplementation is likely to be highly supportive in limiting and resolving the inflammatory process in asthma.

Modulation of the airway smooth muscle phenotype in a murine asthma model and effects of nuclear factor-κB inhibition

Objective: Phenotype modulation of airway smooth muscle (ASM) is a unique characteristic of asthma and is considered to regulate airway remodeling, airway hyperresponsiveness (AHR) and inflammation. The nuclear factor-κB (NF-κB) signaling pathway plays a crucial role in phenotypic modulation. Thus, models of acute and chronic asthma were established and pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor was delivered by intraperitoneal injection. Methods: The Penh value was measured using the BUXCO WBP system. Lung tissues were subjected to histologic analysis. Phenotypic markers of ASM and COL1A1 mRNA levels were measured by RT-PCR. Expression levels of phosphorylated p65 (pP65) and α-SMA were detected by Western blot. Serum cytokine levels were quantified by RayBiotech ELISA array. Results: PDTC intervention decreased the Penh values in both the acute and chronic models. The ASM area and the airway collagen area were decreased in the PDTC intervention group. A decrease in phenotypic markers were detected in both the acute and chronic models in time-dependent manner, and PDTC intervention partially reversed the phenotypic modulation. The effect of PDTC intervention on systemic inflammation was also verified. Conclusion: These results revealed the existence of a dynamic ASM phenotype modulation procedure in asthma development and that targeting NF-κB by PDTC was effective to mitigate ASM phenotype modulation and major asthmatic pathological features.

Expression of Muscarinic Receptors and the Effect of Tiotropium Bromide in Aged Mouse Model of Chronic Asthma.

BackgroundEfficacy and safety of tiotropium bromide, a muscarinic receptor antagonist, in treatment of asthma have been reported. However, its effect on airway remodeling in chronic asthma of the elderly has not been clearly verified. The objective of this study was to investigate the effect of tiotropium and expression of muscarinic receptors as its related mechanism in an aged mouse model of chronic asthma with airway remodeling.MethodsBALB/c female mice age 6 weeks, 9 and 15 months were sensitized and challenged with ovalbumin (OVA) for three months. Tiotropium bromide was administered during the challenge period. Airway hyperresponsiveness (AHR) and pulmonary inflammation were measured. Parameters of airway remodeling, and expression levels of M2 and M3 receptors were examined.ResultsTotal cell with eosinophils, increased in the OVA groups by age, was decreased significantly after treatment with tiotropium bromide, particularly in the age group of 15 months. AHR and levels of interleukin (IL)-4, IL-5, and IL-13 were decreased, after tiotropium administration. In old aged group of 9- and 15-months-treated groups, hydroxyproline contents and levels of α-smooth muscle actin were attenuated. Tiotropium enhanced the expression of M2 but decreased expression of M3 in all aged groups of OVA.ConclusionTiotropium bromide had anti-inflammatory and anti-remodeling effects in an aged mouse model of chronic asthma. Its effects seemed to be partly mediated by modulating expression M3 and M2 muscarinic receptors. Tiotropium may be a beneficial treatment option for the elderly with airway remodeling of chronic asthma.

Effects of Viola tricolor Flower Hydroethanolic Extract on Lung Inflammation in a Mouse Model of Chronic Asthma

Asthma is a chronic inflammatory disease of the lungs driven by T cell activation. Viola tricolor L. as a traditional medical herb could suppress activated T lymphocytes and has been used empirically for asthma remedy. In the present study, we investigated the anti-inflammatory effect of Viola tricolor and its underlying mechanism on asthma characteristics induced by ovalbumin (OVA) in mice. BALB/c mice were randomly divided into six groups: normal control, Ovalbumin (OVA) control, OVA mice treated with Viola tricolor (50, 100 and 200 mg/kg) and dexamethasone (3 mg/kg). All mice except normal controls were sensitized and challenged with OVA. Asthmatic mice were treated orally in the last 7 days of OVA challenge. The total and differential leukocyte counts, Interleukin (IL)-4 and interferon (IFN)-γ levels in bronchoalveolar lavage fluid (BALF) were determined. H and E staining for lung inflammation was performed.Viola tricolor treatment at 200 mg/kg significantly decreased IL-4 level but did not considerably affect the IFN-γ level. Therefore, it effectively reduced asthma characteristics including infiltration of leukocytes particularly eosinophil and peribronchial inflammation as compared to dexamethasone. However, Viola tricolor at 100 mg/kg had the most prominent inhibitory effect on the IL-4 level and also markedly increased IFN-γ level. As result, it prevented further reduction of inflammatory parameters in this group compared to the Viola tricolor-treated group at 200 mg/kg. Our study demonstrated that Viola tricolor has anti-inflammatory effects via inhibition of T-helper type 2 (Th2) cytokine production and validated its empirical usage in traditional medicine.

The Anti-Inflammatory Effects of Fermented Herbal Roots of Asparagus cochinchinensis in an Ovalbumin-Induced Asthma Model.

Introduction: Roots of Asparagus cochinchinensis, which have pharmacologically active ingredients, have received great attention because they show good therapeutic effects for various inflammatory diseases without specific toxicity. This study investigated the anti-asthmatic effects of a butanol extract of Asparagus cochinchinensis roots that had been fermented with Weissella cibaria (BAW) and its possible underlying cholinergic regulation. Methods: Alterations of the anti-asthmatic markers and the molecular response factors were measured in an ovalbumin (OVA)-induced asthma model after treatment with BAW. Results: Treatment with BAW decreased the intracellular reactive oxygen species (ROS) production in lipopolysaccharides (LPS) activated RAW264.7 cells. The results of the animal experiments revealed lower infiltration of inflammatory cells and bronchial thickness, and a significant reduction in the number of macrophages and eosinophils, concentration of OVA-specific IgE, and expression of Th2 cytokines in the OVA + BAW treated group. In addition, a significant recovery of goblet cell hyperplasia, MMP-9 expression, and the VEGF signaling pathway was observed upon airway remodeling in the OVA + BAW treated group. Furthermore, these responses of BAW were linked to recovery of acetylcholine esterase (AChE) activity and muscarinic acetylcholine receptor (mAChR) M3 downstream signaling pathway in epithelial cells, smooth muscle cells, and afferent sensory nerves of OVA + BAW-treated mice. Conclusion: Overall, these findings are the first to provide evidence that the therapeutic effects of BAW can prevent airway inflammation and remodeling through the recovery of cholinergic regulation in structural cells and inflammatory cells of the chronic asthma model.

Petiveria alliacea Suppresses Airway Inflammation and Allergen-Specific Th2 Responses in Ovalbumin-Sensitized Murine Model of Asthma.

To examine the effect of metanol extract of Petiveria alliacea (PM) on airway inflflammation in a murine model of chronic asthma. Two-month-old male BALB/c mice (n=6-8/group) were sensitized on days 0 and 14 by intraperitoneal injection of 20 μg ovalbumin (OVA). On day 25, the mice received an airway challenge with OVA (3%, w/v, in phosphate buffered saline). PM was administered orally by oral gavage to mice at doses of 100, 200 and 400 mg/kg body weight once daily from days 18 to 23. Control mice were orally administered phosphate buffered saline (PBS) to induce a model of asthma. At the end of the test, respiratory reactivity was assayed, the total cell number, interleukin-4 (IL-4), IL-5, IL-13, tumor necrosis factor-alpha (TNF-α) and reactive oxygen species (ROS) in the bronchoalveolar lavage fluid (BALF) were determined and the levels of serum IgE, intercellular cell adhesion molecule 1 (ICAM-1) and eotoxin were measured. In addition, lung tissue was used to qualify the IL-4, IL-5, IL-13, TNF-α and transforming growth factor beta 1 (TGF-β1). Histologic examination was performed to observe inflammatory cellular infiltration. The administration of PM in comparison with the OVA-only treated group signifificantly attenuated the infifiltration of eosinophils and other inflflammatory cells (P<0.01). Airway resistance (RI) in the OVA-only induced group was significantly higher than that of the PBS control group (P<0.01) when methacholine was added. TNF-α, IgE, TGF-β1 and cytokine levels IL-4, IL-5, IL-13 in the BALF decreased compared to control mice (P<0.01 or P<0.05). PM treatment also inhibited the production of chemokines, eotaxin and ICAM-1 in BALF (P<0.01), which improved lung function. Histopathological examination revealed that the sensitized treated PM groups had significant lower in inflammatory scores similar to dexamethasone treatments and the untreated group. Administration of PM could inhibit airway inflammation, regulate cytokines, chemokines and enhance pulmonary conditions in allergic murine model of asthma.

Chronic asthma-induced behavioral and hippocampal neuronal morphological changes are concurrent with BDNF, cofilin1 and Cdc42/RhoA alterations in immature mice

IntroductionRecent studies have found that persistent hypoxia caused by chronic asthma, especially during childhood, affects the development and function of the brain, but the mechanism is unclear. In the present study, BDNF and its signal pathway was investigated in mediating chronic asthma induced-neuronal changes that lead to behavior alterations. MethodsThe chronic asthma model was induced by sensitization with ovalbumin for more than 9 weeks in immature mice. Morris water maze test (MWMT), open field test (OFT) and elevated plus maze test (EPMT) were used to conduct behavioral evaluation. Neuronal morphology in hippocampal CA1, CA3 and DG was assessed using ImageJ's Sholl plugin and RESCONSTRUCT software. BDNF signaling pathway related molecules was determined by Western blotting. ResultsChronic asthma does affect the behavioral performances of immature mice evaluated in MWMT, OFT, and EPMT. The analysis by three-dimensional reconstruction software found that following the behavioral alteration of asthmatic mice, dendritic changes also occurred in hippocampal neurons, including shortened dendrite length, significantly reduced number of dendritic branches, decreased density of dendritic spines, and reduced percentage of functional dendritic spine types. At the same time, by immunofluorescence and western blotting, we also found that alterations in dendritic morphology were consistent with activation of cofilin1 and changes in BDNF-Cdc42/RhoA levels. Some of the changes mentioned above can be alleviated by intranasal administration of budesonide. ConclusionOur data suggest that response similar to nicotine withdrawal or/and hypoxia induced by childhood chronic asthma enhances the BDNF-Cdc42/RhoA signaling pathway and activates cofilin1, leading to the remodeling of actin, causing the loss of dendritic spines and atrophy of dendrites, eventually resulting in behavioral alterations.

Efficacy of an Inhaled IL-13 Antibody Fragment in a Model of Chronic Asthma.

IL-13 is an important cytokine implicated in the pathogenesis of allergic asthma and is an attractive target for an inhaled therapeutic. To investigate the efficacy of CDP7766, a nebulized inhaled anti-IL-13 monoclonal antibody Fab fragment, in a model of allergic asthma in cynomolgus macaques naturally sensitized to Ascaris suum. CDP7766 was nebulized using a vibrating-membrane nebulizer on the basis of eFlow technology. The aerosol generated was analyzed to determine the particle size profile and the biophysical and functional properties of CDP7766. Nebulized CDP7766 (0.1-60 mg/animal, once daily for 5 d) was delivered via the inhaled route. The investigational eFlow nebulizer used in this study generated a respirable aerosol of CDP7766 with no evidence of degradation, loss of potency, aggregation, or formation of particulates. Inhaled CDP7766 was well tolerated in the model (no adverse effects related to local irritation) and significantly inhibited BAL allergen-induced cytokine and chemokine upregulation (60 mg vs. vehicle: eotaxin-3, P < 0.0008; MIP [macrophage inflammatory protein]-1β, IL-8, IFN-γ, P ≤ 0.01). CDP7766 significantly inhibited the increase in pulmonary resistance stimulated by inhaled allergen, measured 15 minutes and 24 hours after allergen challenge. Inhaled CDP7766 potently inhibited the function of IL-13 generated during the airway response to inhaled allergen in cynomolgus macaques, demonstrating the potential of inhaled anti-IL-13 therapeutics for the treatment of allergic asthma.

Progressive increase in allergen concentration abrogates immune tolerance in ovalbumin-induced murine model of chronic asthma

Persistent inflammation and remodeling of airways are the major hallmarks of asthma. Though airway inflammation diminishes in ovalbumin (OVA)-based mouse model of chronic asthma owing to immune-tolerance linked with repeated allergen exposure, which limits the application of the disease model. Accordingly, the present study was designed to develop a murine model of chronic asthma which presents persistent airway inflammation coupled with remodeling traits. Herein, OVA-sensitized BALB/c mice were challenged with increasing (modified protocol) or constant concentration (conventional protocol) of the allergen for 6 weeks; 3 times/week. The results, indeed, revealed that mice subjected to modified protocol demonstrate an improved response to the allergen as reflected by the significant increase in inflammatory cells particularly, eosinophils in bronchoalveolar lavage fluid compared to conventional protocol. Moreover, the expression of Th2 cytokines and their responsible transcription factors (GATA-3 and STAT-6) was markedly enhanced in lungs. The increase in inflammation was further accompanied by a marked increase in mucus production, collagen deposition, and the expression of allied factors (Muc5ac, Col1α1, and α-SMA). Interestingly, pre-treatment of dexamethasone, a corticosteroid (0.5 mg/kg b.wt., i.p.), suppressed the allergen-induced airway inflammation and mucus production without altering collagen deposition. Failure of dexamethasone seems to be related to their ineffectiveness to modulate the expression of TGF-β, MMP-9, COL1α1, and α-SMA. Overall, our results strongly suggest that mice underwent modified chronic protocol bears more resemblance with asthmatics as it imitates persistent airway inflammation allied with steroid-refractory remodeling traits; hence, may be useful for the evaluation of new/alternative drugs in steroid-refractory asthmatic conditions.

The Role of Myristoylated, Alanine-rich C-kinase Substrate (MARCKS) in a Murine Model of Chronic Airway Inflammation

Abstract Severe asthma, a complicate chronic lung inflammation. Several chronic inflammatory cells that involved in the inflammatory responses, such as macrophages, neutrophils, and eosinophils, produce large amounts of ROS, the excess level of ROS would increase lung inflammation and lung injury. In fact, this inflammation is well controlled by steroid, but some subset of patients these glucocorticoids are less effective. Neutrophil recruitment is a prominent feature of acute exacerbations of chronic asthma. In patients with difficult-to-control asthma, neutrophilic inflammation rather than eosinophils often predominate. Myristoylated alanine-rich C kinase substrate (MARCKS), is a protein kinase C (PKC) substrate. MARCKS also plays a crucial role that phosphorylation of MARCKS by PKC leads its release from plasma membrane into the cytosol, participating in regulating cell migration such as macrophage and neutrophil. We found that increase of airway MARCKS phosphorylation in asthmatic patients and murine model of chronic steroid-resistance allergic asthma. In this report, our observations indicate that 1) targeting of MARCKS phosphorylation inhibited chronic asthmatic symptoms, such as eosinophil and neutrophil infiltrate into lung. MPS peptide inhibits mucus production, collagen deposition and airway hyperresponsiveness rather than steroid-resistance group; 2) targeting of MARCKS phosphorylation decreased IFN-r, IL-4, IL-17A, IL-33, eotaxin and KC production. MPS peptide also inhibit NADPH oxidase DUOX-1, 2 protein expression and end product 3-nitrotyrosine production; We found that MPS peptide shows a therapeutic potential for steroid-resistance allergic asthma.

Effects of Educated Monocytes with Xenogeneic Mesenchymal Stem Cell–Derived Conditioned Medium in a Mouse Model of Chronic Asthma

ABSTRACTBackground: This study was conducted to determine the potential of the monocytes educated with rat bone marrow mesenchymal stem cell–derived conditioned medium (MCM) in ameliorating animal model of asthma.Methods: Chronic asthma was induced in the BALB/c mice using ovalbumin (OVA) sensitization. The monocytes were isolated from blood of mice and supplemented with 50% MCM or negative control media. After 24 h, the cells were designated as “non-educated or educated”. Fourteen weeks after the onset of the study, animals were treated with educated or non-educated monocytes twice with a 1-week interval.Results: The educated monocytes showed a reduction in the potential production of the respiratory burst and nitric oxide and the secretion of IL-12 and IL-4 compared to non-educated monocytes. Conversely, these monocytes exhibited a significant increase in the production of IL-10 and TGF-?. Also, the levels of CD68+/CD206+ cells significantly increased in the population of educated monocytes. More importantly, the severity of histopathological lesions, NF-?B p65 mRNA level in lung tissues, total serum IgE and the total cell count, as well as the eosinophil count in the bronchoalveolar lavage fluid, were significantly decreased in OVA-inhaled mice treated with educated monocytes compared to OVA-sensitized group receiving non-educated monocytes. With no advantage in up-regulation of Foxp3 Treg cells, the treatment with educated monocytes reduced the secretion of IL-5 and IL-13 by splenocytes of asthma mice more than splenocytes of the asthma mice treated with non-educated monocytes.Conclusion: The educated monocytes with MCM may be as a promising strategy for cell-based therapies of asthma.

The 4 Position of 5‐HT2A Structural Agonists Imparts the Anti‐Inflammatory Propensity Responsible for Reducing Airway Hyperrresponsiveness in Allergic Asthma

The 5‐HT2A receptor is the most widely expressed serotonin receptor in mammals. While distribution occurs largely in the central nervous system, the 5‐HT2A receptor has been detected in platelets, endothelial and epithelial cells, and lymphatic tissue. Most commonly viewed as the classical target of psychedelic compounds, our lab has made significant progress in understanding how activity at the 5‐HT2A receptor profoundly activates anti‐inflammatory pathways. Here we have generated a chronic asthma model to examine the therapeutic potential of 5‐HT2A receptor activation in persistent allergic airways disease. Our studies show that nasal administration of the 5‐HT2A agonist (R)‐DOI attenuates the elevated airway responsiveness, goblet cell hyperplasia, collagen deposition, and airway structural remodeling that accompanies persistent allergen challenge. Additionally, we have used an acute model in rodents to interrogate structural components of known psychedelics most critical for their anti‐inflammatory effects. Our studies indicate that the 4 position of 5‐HT2A structural agonists contains the chief mediator for reducing bronchial hyperresponsiveness in asthma. This ultimately suggests that a blood‐brain inpenetrant molecule can be developed that lacks the psychoactivity of classical psychedelics but maintains therapeutic efficacy.Support or Funding InformationThis work was supported, in part, by research funds from the American Asthma Foundation Scholar Grant Award to C.N., The Betsey Gordon Foundation, and the Eleusis Benefit Corporation, PBC.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The effects of transient receptor potential channel (TRPC) on airway smooth muscle cell isolated from asthma model mice.

This study aimed to validate whether transient receptor potential channel1 (TRPC1) and TRPC3 participate in the regulation the proliferation of airway smooth muscle cells (ASMCs) through modulating calcium ion (Ca2+ ) influx in vitro. Chronic model of murine asthma was induced and ASMCs isolated from asthmatic mice were used in this whole study. TRPC1 and TRPC3 were upregulated in asthmatic mouse ASMCs and selected for further investigation. Ca2+ concentration and the cell viability of asthmatic mouse ASMCs were significantly higher than that from non- asthma mice, however, TRPC channels blocker SKF96365 alleviated these effects. Furthermore, TRPC1 or TRPC3 overexpression markedly increased Ca2+ concentration and significantly induced the viability of ASMCs; whereas TRPC1 or TRPC3 knockdown exerted the completely conversed effects. Moreover, knockdown of TRPC1 and TRPC3 also exerted different effects on the protein expression of growth-related proteins p-p38, p-JNK, cleaved caspase-3 and Bcl-2, as well as on cell cycle. Finally, we found Ca2+ chelator EGTA or BAPTA-AM significantly diminished the effects of si-TRPC1 and si-TRPC3 on the cell viability, cell cycle, and the protein expression of p-p38, p-JNK, cleaved caspase-3, and Bcl-2 in asthmatic mouse ASMCs. Our findings demonstrated that the effects of TRPC1 and TRPC3 on the cell viability and cell cycle of ASMCs were, at least partially, through regulating Ca2+ influx.

The Effect of Viola Tricolor L. Flower Hydro-Alcoholic Extract on Anxiety-Like Behavior in a Mouse Model of Chronic Asthma

The Effect of Viola Tricolor L. Flower Hydro-Alcoholic Extract on Anxiety-Like Behavior in a Mouse Model of Chronic Asthma

Limethason reduces airway inflammation in a murine model of ovalbumin-induced chronic asthma without causing side effects.

Airway inflammation is the major pathological feature of asthma. Thus, the current therapeutic strategy for asthma is to control inflammation. Limethason, an anti-inflammation drug, is widely used in rheumatoid arthritis treatment. The aim of the present study was to detect the anti-inflammatory effect and side effects of limethason on airways that were sensitized with ovalbumin in a murine model of chronic asthma. In the present study, BALB/c mice were sensitized with ovalbumin. Airway hyperresponsiveness was estimated, and hematoxylin and eosin staining, Periodic acid-Schiff staining and bronchoalveolar lavage were used to detect the effect on chronic asthma. Limethason effectively reduced airway hyperresponsiveness, and inhibited inflammatory cell infiltration and mucus secretion. Bronchoalveolar lavage fluid analysis revealed that limethason suppressed levels of airway eosinophils. In the period of treatment, limethason exhibited no influence on morphology of the femoral head, bone mineral content or bone mineral density, which were detected by histological studies and dual-energy X-ray absorptiometry. The index of liver, spleen, kidney, gastrocnemius and brown adipose tissue also demonstrated that limethason had no adverse effects on organs and tissues. The present study revealed that limethason could effectively reduce inflammation in an asthma mouse model without side effects. Therefore, limethason may have therapeutic potential for treating chronic asthma clinically.

Immuno-modulatory and Therapeutic Effect of Curcumin in an Allergensensitized Murine Model of Chronic Asthma

Background: Asthma is a chronic allergic disease of the lung and airways, characterized by persistent inflammation and airway hyper-responsiveness. More than 200 million people are affected with severe asthma worldwide. T cells, especially Th2 cells, secreting IL-4, IL-5 and IL-13, are pivotal in orchestrating the disease process. We herein investigated the inhibition mechanism of curcumin, a polyphenol present in turmeric, and its ability to alleviate allergic asthma in C57BL/6J mice.Methods: Mice were sensitized and challenged with Ovalbumin for 54 days. We investigated cellular infiltration in blood and BALF, assessed levels of serum IgE, assessed structural changes by histological analysis, and determined the levels of expression of relevant genes and proteins.Results: Our data revealed that curcumin has some anti-inflammatory effect and is successful in ameliorating the disease. We found that curcumin most likely acts by inhibiting the activation of NFκB and its subsequent downstream processes. Our data provided evidence in support of therapeutic application of curcumin in allergic inflammation and airway remodeling.

MicroRNA-485 Modulates the TGF-β/ Smads Signaling Pathway in Chronic Asthmatic Mice by Targeting Smurf2

Chronic respiratory conditions continue to plague millions of people worldwide. We aimed to elucidate the detailed mechanisms of microRNA-485 (miR-485) in airway smooth muscle cell (ASMC) proliferation and apoptosis in chronic asthmatic mice. A mouse model of chronic asthma was established. Ovalbumin was used to induce chronic asthma in the mice. The levels of transforming growth factor β (TGF-β), interleukin (IL)-4, IL-5, IL-13 and IL-17 in bronchoalveolar lavage fluid in mice were measured by enzyme-linked immunoassays (ELISAs). ASMCs were transfected with miR-485 mimic, miR-485 inhibitor and siRNA-Smurf2. The reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analyses were applied to detect the mRNA and protein levels of Smurf2, α-SMA, TGF-β1 and decapentaplegic homolog (Smads). The MTT assay was utilized for cell proliferation, while flow cytometry was conducted to assess cell cycle distribution and apoptosis. Lower expression of miR-485 and higher expression levels of TGF-β1, IL-4, IL-5, IL-13 and IL-17 were detected in mice with chronic asthma. Smurf2 was identified as the target gene of miR-485. Upregulation of miR-485 mimic and downregulation of Smurf2 decreased expression levels of Smurf2, α-SMA, TGF-β1 and Smad3, inhibited cell proliferation and increased apoptosis, while contrary results were observed in ASMCs transfected with miR-485 inhibitor. Overexpressed miR-485 inhibits cell proliferation and promotes apoptosis of ASMCs through the Smurf2-mediated TGF-β/Smads signaling pathway in mice with chronic asthma.

Comparing the effects of fluticasone, anti-IgE and anti-TNF treatments in a chronic asthma model

BackgroundCorticosteroids are used in the treatment of asthma. The aim of this study was to determine the efficacy of anti-IgE and anti-TNF alpha as asthma treatments. MethodsA mouse model of chronic asthma was developed. The fluticasone group was exposed to fluticasone and the anti-IgE and anti-TNF groups were administered anti-IgE or anti-TNF. IL-4, and IgE levels were measured, and histological analysis, pathological analysis and miRNA-126, miRNA-133a analyses were applied. ResultsThe cell concentration in the BAL fluid decreased in all the treatment groups. The rate of perivascular and peribronchial cell infiltration decreased in the lung in the high-dose anti-IgE and anti-TNF groups. Smooth muscle thickness decreased in the lung tissue in the low-dose anti-IgE and anti-TNF groups. Bronchial wall thickness decreased in the lung tissue in the fluticasone+anti-IgE group. The IL-4 level in BAL fluid decreased in the high-dose anti-IgE, fluticasone+anti-IgE and anti-TNF groups. IgE levels increased in the BAL fluid in the high-dose anti-IgE and anti-TNF groups. The lymphocyte level increased in the BAL fluid in the high-dose anti-IgE group. The macrophage level decreased in the BAL fluid in the anti-TNF group. The relative expression of miRNA-126 increased in all groups. The relative expression of miRNA-133a decreased in the placebo and fluticasone groups. The relative expression of miRNA-133a increased in the low-dose anti-IgE, high-dose anti-IgE, fluticasone+anti-IgE and anti-TNF groups. ConclusionsThe results showed that anti-IgE is successful as a treatment. Fluticasone+anti-IgE and anti-TNF were seen to be superior to other therapeutic modalities when used for prophylaxis.

COMPARATIVE STUDY OF ACUTE AND CHRONIC MURINE ASTHMA MODEL IN THE PATHOGENESIS OF ASTHMA

RespirologyVolume 22, Issue S3 p. 89-89 APSR Poster Abstracts COMPARATIVE STUDY OF ACUTE AND CHRONIC MURINE ASTHMA MODEL IN THE PATHOGENESIS OF ASTHMA First published: 20 November 2017 https://doi.org/10.1111/resp.13207_6Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume22, IssueS3Supplement: 22nd Congress of the Asian Pacific Society of Respirology, International Convention Centre, Sydney, Australia, 23–26 November 2017November 2017Pages 89-89 RelatedInformation