Development Of Allergic Asthma Research Articles

Invariant NKT Cells Act as an Adjuvant to Enhance Th2 Inflammatory Response in an OVA-Induced Mouse Model of Asthma

BackgroundInvariant natural killer T cells (iNKT cells) are a unique subset of T lymphocytes and are considered to play an important role in the development of allergic bronchial asthma. Recently, iNKT cells were shown to play an immunoregulatory role in CD4+ and CD8+ T cell-mediated adaptive immune response. Allergen-specific Th2 inflammatory responses are an important part of the adaptive immune response in asthma. However, the regulatory functions of the Th2 inflammatory response in asthma have not been studied in detail.MethodIn this study, we have investigated the regulatory functions of iNKT cells on the Th2 inflammatory response in an ovalbumin (OVA)-induced murine model of asthma.ResultsOur results demonstrate that α-Galactosylceramide (α-GalCer) administration activated iNKT cells but could not induce the Th2 inflammatory response in wild-type (WT) mice. In the OVA-induced asthma model, α-GalCer administration and adoptive transfer of iNKT cells significantly augmented the Th2 inflammatory responses, including elevated inflammatory cell infiltration in the lung and bronchoalveolar lavage fluid (BALF); increased levels of IL-4, IL-5, and IL-13 in the BALF and splenocyte culture supernatant; and increased serum levels of OVA-specific IgE and IgG1. In addition, the Th2 inflammatory response was reduced, but not completely abrogated in CD1d-/- mice immunized and challenged with OVA, compared with WT mice.ConclusionThese results suggest that iNKT cells may serve as an adjuvant to enhance Th2 inflammatory response in an OVA-induced murine model of asthma.

Microbiome in Inner‐City Asthma

Prevalence of childhood asthma has increased dramatically over the past several decades in Western nations, and particularly in inner city populations. Evidence has emerged for both local environmental exposure in infancy and early life gut microbiome disturbances as associated with childhood allergic asthma development. This has led to the hypothesis that the house dust microbial environment of infants may influence their developing gut microbiome in a manner that alters the risk for childhood allergic disease and asthma development. We have recently demonstrated that house dust microbiome composition varies across inner‐city homes and that this variability is significantly related to allergic disease development in children raised in these environments. Children who develop atopy and recurrent wheezing at age three lack environmental microbial exposures in their house dust that are encountered by children who do not develop these disease phenotypes. The majority of these organisms enriched in allergy‐protective households have been previously described in the human gut microbiome. Moreover, murine studies have demonstrated that exposure of mice to dust from allergy protective households, alters the composition of the gut microbiome in a manner that protects against airway allergen challenge. A specific species, Lactobacillus sakei, found to be significantly enriched in the gut microbiome of these protected animals, was capable of conferring airway protection against both allergen and respiratory viral infection in animals supplemented orally with this species. Hence the growing evidence supports a strong role for household microbial exposures as playing a role in shaping gut microbiome composition in early infancy, in a manner that influences mucosal adaptive responses to a variety of airway insults.

Cutting edge: STAT6 signaling in eosinophils is necessary for development of allergic airway inflammation.

Eosinophils are critical cellular mediators in allergic asthma and inflammation; however, the signals that regulate their functions are unclear. The transcription factor STAT6 regulates Th2 cytokine responses, acting downstream of IL-4 and IL-13. We showed previously that eosinophil-derived IL-13 plays an important role in the recruitment of T cells to the lung and the subsequent development of allergic asthma. However, whether eosinophils respond to Th2 signals to control allergic airway inflammation is unclear. In this report, we show that STAT6(-/-) eosinophils are unable to induce the development of allergic lung inflammation, including recruitment of CD4(+) T cells, mucus production, and development of airways hyperresponsiveness. This is likely due to the reduced migration of STAT6(-/-) eosinophils to the lung and in response to eotaxin. These data indicate that, like Th cells, eosinophils need to respond to Th2 cytokines via STAT6 during the development of allergic airway inflammation.

Exposure to allergen and diesel exhaust particles potentiates secondary allergen-specific memory responses, promoting asthma susceptibility

Exposure to traffic pollution particulate matter, predominantly diesel exhaust particles (DEPs), increases the risk of asthma and asthma exacerbation; however, the underlying mechanisms remain poorly understood. We sought to examine the effect of DEP exposure on the generation and persistence of allergen-specific memory T cells in asthmatic patients and translate these findings by determining the effect of early DEP exposure on the prevalence of allergic asthma in children. The effect of DEPs on house dust mite (HDM)-specific memory responses was determined by using an asthma model. Data from children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study birth cohort were analyzed to determine the effect of DEP exposure on asthma outcomes. DEP coexposure with HDM resulted in persistent TH2/TH17 CD127(+) effector/memory cells in the lungs, spleen, and lymph nodes of adult and neonatal mice. After 7 weeks of rest, a single exposure to HDM resulted in airway hyperresponsiveness and increased TH2 cytokine levels in mice that had been previously exposed to both HDM and DEPs versus those exposed to HDM alone. On the basis of these data, we examined whether DEP exposure was similarly associated with increased asthma prevalence in children in the presence or absence of allergen exposure/sensitization in the Cincinnati Childhood Allergy and Air Pollution Study birth cohort. Early-life exposure to high DEP levels was associated with significantly increased asthma prevalence among allergic children but not among nonallergic children. These findings suggest that DEP exposure results in accumulation of allergen-specific TH2/TH17 cells in the lungs, potentiating secondary allergen recall responses and promoting the development of allergic asthma.

Obesity increases airway hyperresponsiveness via the TNF-α pathway and treating obesity induces recovery.

Obesity is a known risk factor for allergic asthma. It has been recognized as a key player in the pathogenesis of several inflammatory disorders via activation of macrophages, which is also vital to the development of allergic asthma. We investigated the mechanism of obesity-related asthma and whether treating obesity through exercise or diet ameliorates the severity of asthma in the obesity-related asthma model. We generated diet-induced obesity (DIO) in C57BL/6 mice by high-fat-feeding and ovalbumin-induced asthma (lean-OVA or DIO-OVA). The DIO-OVA mice were then treated with tumor necrosis factor (TNF)-α neutralizing antibody as a TNF-α blockade or a Cl2MDP-containing liposome to induce an alveolar macrophage deficiency. To treat obesity, the DIO-OVA mice were under dietary restrictions or exercised. The pathophysiological and immunological responses were analyzed. Airway hyperresponsiveness (AHR), serum IgE and TNF-α levels in the lung tissue increased in the DIO-OVA mice compared to the lean-OVA mice. Both the TNF-α blockade and depletion of alveolar macrophages in the DIO-OVA mice decreased AHR compared to the DIO-OVA mice. Treating obesity by exercise or through dietary means also reduced pulmonary TNF-α levels and AHR in the DIO-OVA mice. These results suggest that restoring normal body weight is an appropriate strategy for reducing TNF-α levels, and controlling inflammation may help improve asthma severity and control in obesity-related asthma.

Alterations of the Murine Gut Microbiome with Age and Allergic Airway Disease.

The gut microbiota plays an important role in the development of asthma. With advanced age the microbiome and the immune system are changing and, currently, little is known about how these two factors contribute to the development of allergic asthma in the elderly. In this study we investigated the associations between the intestinal microbiome and allergic airway disease in young and old mice that were sensitized and challenged with house dust mite (HDM). After challenge, the animals were sacrificed, blood serum was collected for cytokine analysis, and the lungs were processed for histopathology. Fecal pellets were excised from the colon and subjected to 16S rRNA analysis. The microbial community structure changed with age and allergy development, where alterations in fecal communities from young to old mice resembled those after HDM challenge. Allergic mice had induced serum levels of IL-17A and old mice developed a greater allergic airway response compared to young mice. This study demonstrates that the intestinal bacterial community structure differs with age, possibly contributing to the exaggerated pulmonary inflammatory response in old mice. Furthermore, our results show that the composition of the gut microbiota changes with pulmonary allergy, indicating bidirectional gut-lung communications.

Distinct roles of the anaphylatoxins C3a and C5a in dendritic cell-mediated allergic asthma.

Conventional dendritic cells (cDC) are necessary and sufficient to drive mixed maladaptive Th2/Th17 immune responses toward aeroallergens in experimental allergy models. Previous studies suggest that the anaphylatoxin C3a promotes, whereas C5a protects from the development of maladaptive immunity during allergen sensitization. However, only limited evidence exists that such effects are directly mediated through anaphylatoxin-receptor signaling in cDCs. In this study, we assessed the impact of C3a and C5a on cDC-mediated induction pulmonary allergy by adoptively transferring house dust mite (HDM)-pulsed bone marrow-derived DCs (BMDC) from wild-type (WT) C3aR(-/-), C5aR1(-/-), or C3aR(-/-)/C5aR1(-/-) into WT mice. Transfer of HDM-pulsed WT BMDCs promoted a strong asthmatic phenotype characterized by marked airway resistance, strong Th2 cytokine, and mucus production, as well as mixed eosinophilic and neurophilic airway inflammation. Surprisingly, C3aR(-/-) cDCs induced a strong allergic phenotype, but no IL-17A production, whereas HDM-pulsed C5aR1(-/-) cDCs failed to drive pulmonary allergy. Transfer of C3aR(-/-)/C5aR1(-/-) cDCs resulted in a slightly reduced allergic phenotype associated with increased IFN-γ production. Mechanistically, C3aR and C5aR1 signaling is required for IL-23 production from HDM-pulsed BMDCs in vitro. Furthermore, C3aR(-/-) BMDCs produced less IL-1β. The mechanisms underlying the failure of C5aR1(-/-) BMDCs to induce experimental allergy include a reduced capability to migrate into the lung tissue and a decreased potency to direct pulmonary homing of effector T cells. Thus, we uncovered a crucial role for C5a, but only a minor role for C3a in BMDC-mediated pulmonary allergy, suggesting that BMDCs inappropriately reflect the impact of complement on lung cDC-mediated allergic asthma development.

Thymic stromal lymphopoietin signaling in CD4+ T cells is required for TH2 memory

Thymic stromal lymphopoietin (TSLP) is a key factor in the development of allergic asthma. Numbers of TH2 memory cells gradually increase in allergic patients with the progression of disease and persist in the lungs during remission, although the mechanism is not clear. We sought to define the role of TSLP in TH2 memory cell generation and maintenance in vivo. Adoptive transfer of wild-type and thymic stromal lymphopoietin receptor (TSLPR)-deficient ovalbumin-specific CD4(+) T cells before TH2 sensitization was used to define T cell-specific TSLP effects. Atopic dermatitis and increased serum TSLP concentrations were induced by topical application of the vitamin D3 analog MC903. Memory cells in peripheral blood were monitored weekly with flow cytometry. Memory recall was tested after intranasal ovalbumin challenge. TSLP signaling in CD4(+) T cells is required for the generation/maintenance of memory cells after in vivo priming. TSLPR-deficient CD4(+) T cells have no defects in proliferation but do not survive 1 week after sensitization, and increased TSLP expression during sensitization significantly increased the frequency of memory cells. Although in vitro-differentiated TSLPR-deficient TH2 cells develop into memory cells with equal efficiency to wild-type cells, the recall response to airway antigen challenge is impaired. Moreover, after antigen challenge of mice with established TH2 memory, TSLP signaling in CD4(+) T cells significantly affects memory cell generation/maintenance from secondary effector cells. TSLP signaling in CD4(+) T cells is required for not only TH2 memory cell formation in vivo but also the recall response of the memory cells to local antigen challenge.

The intestinal microbiota and allergic asthma

There is increasing evidence that environmental changes are involved in the sharp increase in asthma incidence, as well as with other immune-mediated diseases. This increase matches the introduction of modern life advances such as antibiotics and caesarean sections. Several epidemiological studies provide convincing evidence that a lack of exposure to microbes early in life is associated with later development of allergic asthma. In addition, animal studies have shown that early life modulation of the intestinal microbiota with antibiotics has profound effects in the immune cellular mechanisms that lead to asthma. By describing some of the most relevant human and animal studies in this field, we explore the concept that significant perturbations of the intestinal and perhaps the lung microbiota are a cause of allergic asthma.

Environmental tobacco smoke exposure and risk of allergic sensitisation in children: a systematic review and meta-analysis

BackgroundEnvironmental tobacco smoke (ETS) exposure in children is linked with the development of allergic asthma. However, its influence on allergic sensitisation in children has not been conclusively determined.ObjectiveTo systematically review...

Lifetime-dependent effects of bisphenol A on asthma development in an experimental mouse model.

BackgroundEnvironmental factors are thought to contribute significantly to the increase of asthma prevalence in the last two decades. Bisphenol A (BPA) is a xenoestrogen commonly used in consumer products and the plastic industry. There is evidence and an ongoing discussion that endocrine disruptors like BPA may affect human health and also exert alterations on in the immune system. The aim of this study was to investigate age-dependent effects of BPA on the asthma risk using a murine model to explain the controversial results reported till date.MethodsBALB/c mice were exposed to BPA via the drinking water for different time periods including pregnancy and breastfeeding. To induce an asthma phenotype, mice were sensitized to ovalbumin (OVA), followed by an intrapulmonary allergen challenge.ResultsBPA exposure during pregnancy and breastfeeding had no significant effect on asthma development in the offspring. In contrast, lifelong exposure from birth until the last antigen challenge clearly increased eosinophilic inflammation in the lung, airway hyperreactivity and antigen-specific serum IgE levels in OVA-sensitized adult mice compared to mice without BPA exposure. Surprisingly, BPA intake during the sensitization period significantly reduced the development of allergic asthma. This effect was reversed in the presence of a glucocorticoid receptor antagonist.ConclusionsOur results demonstrate that the impact of BPA on asthma risk is strongly age-dependent and ranges from asthma-promoting to asthma-reducing effects. This could explain the diversity of results from previous studies regarding the observed health impact of BPA.

Ganoderma formosanum polysaccharides attenuate Th2 inflammation and airway hyperresponsiveness in a murine model of allergic asthma.

Allergic asthma is an inflammatory disease of the airways mediated by Th2 immune responses and characterized by airway hyperresponsiveness (AHR). Fungi of the genus Ganoderma are basidiomycetes that have been used in traditional Asian medicine for centuries. We recently found that PS-F2, a polysaccharide fraction purified from the submerged culture broth of Ganoderma formosanum, stimulates the activation of dendritic cells and primes a T helper 1 (Th1)-polarized adaptive immune response. This study was designed to investigate whether the Th1 adjuvant properties of PS-F2 could suppress the development of allergic asthma in a mouse model. BALB/c mice were sensitized by repeated immunization with chicken ovalbumin (OVA) and alum, followed by intranasal challenge of OVA to induce acute asthma. PS-F2 administration during the course of OVA sensitization and challenge effectively prevented AHR development, OVA-specific IgE and IgG1 production, bronchial inflammation, and Th2 cytokine production. Our data indicate that PS-F2 has a potential to be used for the prevention of allergic asthma.Electronic supplementary materialThe online version of this article (doi: 10.1186/2193-1801-3-297) contains supplementary material, which is available to authorized users.

Synthetic di-sulfated iduronic acid attenuates asthmatic response by blocking T-cell recruitment to inflammatory sites.

Identification of carbohydrate sequences that determine affinity to specific chemokines is a critical step for strategies to interfere with chemokine-mediated leukocyte trafficking. Here, we first characterized the development of allergic asthma in Tie2-dependent and inducible Ext1-knockout (Tie2-Ext1(iKO)) mice. We showed that heparan sulfate is essential for leukocyte recruitment in the peribronchial region and bronchoalveolar lavage fluid (BALF), and is crucial for induction of airway hyperresponsiveness. Our glycan microarray showed a unique affinity profile of chemokine CCL20 to substructures of heparin and heparin-like oligo/di/monosaccharides. Among them, we identified a synthetic and not naturally occurring monosaccharide, 2,4-O-di-sulfated iduronic acid (Di-S-IdoA), as a potential inhibitor for CCL20-heparan sulfate interaction. Mice injected with Di-S-IdoA via tail vain or nasal inhalation showed attenuated leukocyte recruitment into inflammatory sites and BALF. These results demonstrate a critical role of chemokine-heparan sulfate interaction in the asthma development and Di-S-IdoA as a potential drug for asthma treatment.

PRS68 - Pharmacoeconomic Considerations For Allergen Specific Immunotherapy In A Geopardized Reimbursement Situation: The Italian Case

Allergic rhinoconjuntivitis is a global health problem, and many studies have shown an important increase in the disease prevalence in the last 20 years. Allergen specific immunotherapy (SIT) is the only available treatment for the underlying cause of the disease. At present, few economic evaluations are available for Italy. The present study is focused on the cost effectiveness of SIT in Italy, considering the fragmented reimbursement policies in different Regions of the Country. A review of the literature on the pharmaco-economy of immunotherapy for allergic rhinoconjuntivitis with a special focus on Italy (costs taken from Italian formularies, tariffs and Diagnosis Related Groups, or DRG). Reimbursement values were taken from official regional resolutions Treatment with SIT reduced by 38% symptomatic drugs consumption (whose costs are ranging from € 0.1 to € 0.5 per unit). Moreover, SIT reduced by 30% symptoms intensity (impacting on GPs and specialists visits, whose cost are ranging from € 13 to € 18, respectively) and by 20% the development of allergic asthma (which implies € 190 for one day of hospitalization). There are wide differences in SIT reimbursement across Italian Regions, ranging from 100% in 3, to various level of copayment in 7, down to no reimbursement in 10. Overall, these data support the favorable impact of SIT on the medium-long term in front of a relative cost increase in the short term. This benefit is still not fully recognized in Italy where differences persist across regions in the access to SIT reimbursement.

Signaling pathways in eosinophils that regulate allergic asthma and inflammation (HYP7P.304)

Abstract Allergic asthma and inflammation is a disease of the airways. The prevalence of allergic responses and asthma are increasing worldwide, but it is still unclear why some predisposed individuals develop disease. Eosinophils and T helper 2 cells (TH2) and eosinophils are critical cellular mediators in asthma. The signal transducer and activator of transcription (STAT)-6 is a crucial mediator of TH2 cytokine responses, acting downstream of interleukin -4 and -13 (IL-4 and IL-13). We have previously shown that eosinophil derived IL-13 plays an important role in the recruitment of T cells to the lung, and subsequent development of allergic asthma. However whether eosinophils respond to TH2 signals to control allergic airway inflammation is unclear. The objective of this study is to understand the role of STAT6 in eosinophil-dependent regulation of allergic asthma and inflammation. Using ΔdblGATA mice lacking eosinophils and transfer of STAT6-/- eosinophils, we found that compared to ΔdblGATA reconstituted with WT eosinophils, eosinophils lacking STAT6 were unable to rescue recruitment of CD4+ T cells and eosinophils into the lungs compared to WT eosinophils. These data indicates that STAT6 is important in the recruitment of both T cells and eosinophils to the lung during the development of allergic airway inflammation. Ultimately, deciphering the mechanisms of intracellular and cytokine signals will afford us improved insights on developing therapeutic strategies in asthma.

Mechanisms of pathogenesis in allergic asthma: role of interleukin-23.

Asthma is a chronic airway inflammatory disease characterized by intense leukocyte and eosinophilic infiltration accompanied by mucus hypersecretion and tissue hyperresponsiveness. Recent evidence suggests that T-helper (Th)2 cells and their cytokine products orchestrate the pathology of asthma. In addition, Th17 cells are implicated in the pathogenesis of antigen-induced airway inflammation. The Th17 related cytokine interleukin (IL)-23 plays important roles in many immunological diseases, such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, psoriasis and inflammatory bowel disease. Several reports describe the role of IL-23 in the pathogenesis of allergic asthma in both human and mice. IL-23 leads to neutrophil infiltration in the airway of asthmatic mice, which is characteristic of severe asthma resulting from Th17 development and subsequently IL-17 secretion. IL-23 can also promote eosinophil infiltration in the airway, which is a hallmark of allergic asthma. These studies suggest that IL-23 could be a promoting factor in the development of allergic asthma and likewise would be a target for asthma therapy. In support of this view, trials of anti-IL-23 therapy have been attempted in human and mouse asthma models with encouraging outcomes. This review presents the role of IL-23 in asthma according to recent clinical trials and animal model studies. The proposed mechanisms of IL-23-induced airway inflammation and the agents currently being tested that target IL-23 related pathways are discussed.

Serotonin 5‐HT2 receptor activation prevents the development of allergic asthma: Physiology and functional selectivity (LB575)

Activation of serotonin 5‐HT2A receptors has potent anti‐inflammatory effects in multiple tissues including the nd vasculature and gut. Much of these effects in whole body are through blockade of TNF‐α mediated inflammation. We have found that activation of serotonin 5‐HT2 receptors in the lung with the agonist (R)‐DOI completely blocks the development of allergic asthma in the mouse ovalbumin model. At doses of 0.01 mg/kg inhaled, airways hyperresponsiveness, lung inflammation, mucus overproduction, and eosinophilia are blocked. The molecular and cellular mechanisms underlying these effects are currently under investigation. Structure/activity studies indicate that only phenethylamine 5‐HT2 receptor agonists closely related in structure to (R)‐DOI (e.g. R‐DOM and R‐DOB) are effective in preventing the development of asthma in our model. Phenethylamine agonists more dissimilar in structure are less effective, and indoleamine agonists like lysergic acid diethylamide are ineffective. Our results indicate that phenethylamines similar to (R)‐DOI potentially represent a novel small molecule therapeutic class for the treatment of asthma as well other inflammatory diseases.Grant Funding Source: Supported by NIHR21HL095961, the American Asthma Foundation, and the Heffter Research Institute

Economic evaluation of SQ-standardized grass allergy immunotherapy tablet (Grazax(®)) in children.

BackgroundGrass pollen-induced rhinoconjunctivitis is a common allergic respiratory disorder affecting over 20% of the UK population in terms of quality of life and sleep, work, and school patterns. The SQ-standardized grass allergy immunotherapy tablet (AIT) has been demonstrated as a disease-modifying treatment which gives a sustained effect even after completion of a treatment course. The objective of this study was to provide an economic assessment of whether treatment with the SQ-standardized grass AIT, Grazax® (Phleum pratense) in combination with symptomatic medications is preferable to the standard of care using symptomatic medications only. The analysis was performed for children with grass pollen-induced rhinoconjunctivitis, with or without concomitant asthma, in the UK.MethodsThe model evaluated the two treatment regimens in a cohort of 1,000 children from a payer’s perspective. Treatment was modeled in terms of management of symptoms, impact on resource use, and development of allergic asthma. The analysis modeled the use of SQ-standardized grass AIT and the sustained effects of treatment over a 9-year time horizon (ie, 3 years of treatment, with modeled long-term benefits). Data inputs were drawn from a recent clinical trial, published studies, and databases.ResultsSQ-standardized grass AIT improves patient outcomes, generating an incremental cost per quality-adjusted life year gained of £12,168. This is below commonly accepted thresholds in the UK.ConclusionThe resulting incremental cost per QALY falls below commonly accepted willingness to pay thresholds. Therefore, the SQ-standardized grass AIT is a cost-effective option for the treatment of grass pollen-induced rhinoconjunctivitis in the UK pediatric population.

Infection with respiratory syncytial virus influences FasL-mediated apoptosis of pulmonary γδ T cells in a murine model of allergen sensitization

Background: It has been reported that adoptive transfer of γδ T cells increases the cellular infiltration, especially eosinophils, in the lungs of allergic mice, suggesting that γδ T cells may play a proinflammatory role in allergic airway inflammation. Respiratory syncytial virus (RSV) infection can decrease the number of Th2-type γδ T cells. However, the underlying mechanisms remain unknown. Methods: BALB/c mice were inoculated intranasally with RSV before or after sensitization to OVA. The amounts of Th1/Th2 cytokines as well as the levels of specific antibodies were determined by ELISA. The apoptotic death of pulmonary γδ T cells was analyzed by flow cytometry. Results: Adoptive transfer of γδ T cells increased the production of Th2 cytokines in the lungs and allergy-related antibodies in the serum, further confirming that γδ T cells act as pro-inflammatory cells or a promoter for the development of allergic asthma. RSV infection before sensitization to OVA enhanced apoptotic death of pulmonary γδ T cells. The percentage and absolute number of FasL-expressing γδ T cells in the lungs of allergic mice were elicited significantly by prior RSV infection. Blocking FasL with monoclonal antibody diminished apoptotic death of γδ T cells, suggesting that FasL is important for RSV-induced apoptosis of pulmonary γδ T cells. Conclusions: This work provides evidence that RSV infection suppresses the subsequent development of OVA-induced allergic responses partly by enhancing FasL-mediated apoptosis of pulmonary γδ T cells.

Effects of microRNA-21 on the interleukin 12/signal transducer and activator of transcription 4 signaling pathway in asthmatic mice

ObjectiveTo study the effect of microRNA-21 (miRNA-21) on the regulation of the interleukin 12 (IL-12)/signal transducer and activator of transcription 4 (STAT4) pathway in the lung tissue of asthmatic mice.Material and methodsForty five male C57BL/6 mice were randomly divided into three groups of 15 mice each: normal control, asthmatic model, and dexamethasone. Our mouse model of allergic asathma was established using OVA sensitization and challenge. Hematoxylin and eosin staining was performed to observe the pathological changes in lung tissue morphology. Both the total cell number and the amount of eosinophils (EOS) in the bronchoalveolar lavage fluid (BALF) were manually counted. The expression of miRNA-21 was detected by real time quantitative PCR. The expression levels of IL-12 and STAT4 in lung tissue were assayed via western blot, and immunohistochemistry was used to observe the distribution of their expression.ResultsThe expression levels of miRNA-21 as well as the total number of BALF cells and EOS were significantly higher in the asthmatic model group than in the control or dexamethasone groups, with significantly higher amounts found in the dexamethasone group than in the control group. The expression levels of IL-12 and STAT4 proteins were lower in the asthmatic model group than in the control and dexamethasone groups, with a significantly lower expression of IL-12 and STAT4 in the dexamethasone group than in the control group.ConclusionsThe expression level of miRNA-21 was significantly increased and the expression level of IL-12 and STAT4 proteins was significantly decreased in allergic asthmatic mice compared with normal control mice. These findings suggest a role for miRNA-21 and the IL-12/STAT4 pathway in the development of allergic asthma.