Vitamin D3 levels and NLRP3 expression in murine models of obese asthma: association with asthma outcomes

Vitamin D (25(OH)D3) is an essential nutrient that plays a role in the immune system. Serum 25(OH)D3 is found to be associated with asthma. However, the role of vitamin D in obese asthma remains unclear. Therefore, we investigated the association between vitamin D levels and asthma outcomes in a murine model of obese asthma. We also evaluated NLRP3 inflammasome activity in the pathogenesis of obese asthma. We divided 20 male Balb/c mice (3-4 weeks old) into 4 groups: normal control, asthma, obese, and obese asthma and developed an obese asthma mouse model. Airway hyperreactivity, cytokine concentrations, 25(OH)D3 levels, NLRP3 mRNA and IL-1β mRNA expressions were measured. Lung histology and bronchoalveolar lavage fluid (BALF) cell count were also determined. Obese asthma mice showed a significant increase in airway hyper-responsiveness, airway inflammation, pro-inflammatory cytokine levels and NLRP3 mRNA, IL-1β mRNA expression. Both asthma and obese groups had lower 25(OH)D3 levels. Vitamin D levels in obese asthma were the lowest among all groups. Vitamin D levels correlated negatively with body weight, lung resistance levels at 25 mg/mL of methacholine, total inflammatory cells, and IL-1β and IL-17 concentrations in BALF. These data demonstrated an association between serum vitamin D levels and outcomes of obese asthma, and indicated that NLRP3 inflammasome may play a role in this disorder.

Innate immunity in asthma

Asthma is a complex and heterogeneous disease with several phenotypes. Most studies have focused on allergic asthma associated with allergen sensitization and adaptive immunity. On the other hand, nonallergic asthma is associated with a number of environmental factors such as infection, air pollution, or obesity, and requires innate immunity rather than adaptive immunity. In the lung, a number of innate immune cells and mechanisms have evolved to lead lung inflammation and asthma. These innate mechanisms include innate cytokines and various innate cells, including innate lymphoid cells, natural killer cells, as well as gammadelta T cells, which together produce a wide range of cytokines, independent of adaptive immunity and conventional antigens. Here, we review the most recent works regarding innate immune cells and the mechanisms underlying their role in asthma.

The Roles of Innate Lymphoid Cells in the Development of Asthma

Asthma is a common pulmonary disease with several different forms. The most studied form of asthma is the allergic form, which is mainly related to the function of Th2 cells and their production of cytokines (IL-4, IL-5, and IL-13) in association with allergen sensitization and adaptive immunity. Recently, there have been many advances in understanding non-allergic asthma, which seems to be related to environmental factors such as air pollution, infection, or even obesity. Cells of the innate immune system, including macrophages, neutrophils, and natural killer T cells as well as the newly described innate lymphoid cells, are effective producers of a variety of cytokines and seem to play important roles in the development of non-allergic asthma. In this review, we focus on recent findings regarding innate lymphoid cells and their roles in asthma.

Effective Microorgainsm (EM) Fermentation Extract Attenuates Airway Hyperreactivity and Lung Inflammation In A Mouse Model of Asthma

Effective microorganism (EM) fermentation extract has been widely used for agricultural and environmental application. It has been recently revealed that EM cocktail treatment may be effective for treatment of diseases including cancer. In the present study, effectiveness of EM cocktail to control asthma was investigated using a mouse model of allergic asthma. Asthmatic mice sensitized and intranasally challenged with OVA were orally given EM fermentate (EM-1(R) during antigen challenge. Administration of EM-1(R) resulted in a significant reduction in airway hyper-reactivity (AHR) and airway recruitment of total leukocytes and eosinophils. Cytokine (IL-4, IL-5 and IFNgamma) levels in bronchoalveolar lavage fluid (BALF) and lung tissues were not altered by EM-1(R) treatment. However, IL-13 level in BALF was considerably lower in EM-1(R) treated mice than in controls. Moreover, Ag-specific IL-4, IL-5 and IL-13 production of draining lymph node cells were markedly downregulated by EM-1(R) treatment when compared to controls, whereas their IFNgamma production was not significantly different. Those data show that EM-1(R) treatment suppresses type 2 helper T (Th2), but not type 1 helper T (Th1), cell response. This finding was also supported by serum antibody data showing that IgE and IgG1 levels in EM-1(R) treated mice were significantly lower than in controls, while IgG2a level was not significantly different between two groups. In conclusion, oral administration of EM-1(R) attenuates asthmatic manifestations including AHR and airway recruitment of eosinophils in a mouse model and which possibly results from selective inhibition of Th2 cell response to allergen. Our data also suggest that EM-1(R) may be effectively applied for control of allergic asthma.

Effective Microorgainsm (EM) Fermentation Extract Attenuates Airway Hyperreactivity and Lung Inflammation In A Mouse Model of Asthma

Effective microorganism (EM) fermentation extract has been widely used for agricultural and environmental application. It has been recently revealed that EM cocktail treatment may be effective for treatment of diseases including cancer. In the present study, effectiveness of EM cocktail to control asthma was investigated using a mouse model of allergic asthma. Asthmatic mice sensitized and intranasally challenged with OVA were orally given EM fermentate (EM-1(R) during antigen challenge. Administration of EM-1(R) resulted in a significant reduction in airway hyper-reactivity (AHR) and airway recruitment of total leukocytes and eosinophils. Cytokine (IL-4, IL-5 and IFNgamma) levels in bronchoalveolar lavage fluid (BALF) and lung tissues were not altered by EM-1(R) treatment. However, IL-13 level in BALF was considerably lower in EM-1(R) treated mice than in controls. Moreover, Ag-specific IL-4, IL-5 and IL-13 production of draining lymph node cells were markedly downregulated by EM-1(R) treatment when compared to controls, whereas their IFNgamma production was not significantly different. Those data show that EM-1(R) treatment suppresses type 2 helper T (Th2), but not type 1 helper T (Th1), cell response. This finding was also supported by serum antibody data showing that IgE and IgG1 levels in EM-1(R) treated mice were significantly lower than in controls, while IgG2a level was not significantly different between two groups. In conclusion, oral administration of EM-1(R) attenuates asthmatic manifestations including AHR and airway recruitment of eosinophils in a mouse model and which possibly results from selective inhibition of Th2 cell response to allergen. Our data also suggest that EM-1(R) may be effectively applied for control of allergic asthma.

Study Progress on Change of Small Airway Function in Children with Asthma / 实用儿科临床杂志

Asthma is one kind of chronic respiratory tract inflammatory disease.Recently,it has been discovered that the small airway also participates in asthmatic pathogenesis.The small airway which diameter is less than 2 mm is one of the smallest regions in the lung.Its function may be affected by the small airway disease and related with the airway hyperresponsiveness.Some structural changes in the small airway is the latent reason which aggravates asthma.The change of small airway function in the mild asthma can cause the change of airway hyperresponsiveness.So it is considered that the small airway function is one of the methods to monitor the asthmatic situation.

Effects of ozone on influenza virus-induced airway hyperreactivity in rats / 천식및알레르기

BACKGROUND: Ozone is one of the most ubiquitous oxidant in urban air and may exacerbate respiratory diseases such as asthma. OBJECTIVE: We examined whether ozone can influence airway hyperresponsiveness induced by influenza virus-infection. SUBJECT AND METHOD: Rats were exposed to ozone, acutely to 1.0ppm and 0.25ppm for 23.5hrs. At 2hrs post cessation of ozone exposure, animals were infected with rat-adapted influenza virus intra-nasally. On day 3 post-virus inoculation, pulmonary mechanics were measured during an intravenous challenge with acetylcholine . Cumulative doseresponse functions were obtained by doubling the rate of the intravenous infusion every 2min. RESULTS: ACh increased airway resistance in a dose-dependent manner. Neither of the concentrations of ozone altered the airway responses to ACh. Animals infected with virus developed hyperresponsiveness to ACh as was expected. Pre-exposure to 1.0ppm ozone for 23.5hrs aug- mented the virus-induced airway hyperresponsiveness, while 0.25ppm did not. CONCLUSION: Acute exposure to ozone can synergistically act on virus-induced airway hyperreactivity.

Influenza virus-induced airway hyperreactivity in rats / 천식및알레르기

BACKGROUND AND OBJECTIVE: Studies indicate that humans infected with influenza virus manifest a post-virus increase in airway responsiveness. Therefore, whether influenza virus would cause airway hyperreactivity was investigated. SUBJECT AND METHOD: Rats were infected with rat-adapted influenza virus via nasal instillation. On days 1, 2, 3, 5, 7 and 9 post-virus inoculation, pulmonary mechanics were measured during an intravenous challenge with acetylcholine (ACh, 100-140 mg/ml saline). Cumulative dose-response functions were obtained by doubling the rate of the infusion every 2 minutes. RESULTS: ACh increased airway resistance and decreased dynamic compliance in a dosedependent manner. The airway responses to ACh was enhanced in most animals challenged 3 days after the inoculation. About half of the animals challenged 2 and 5 days after the virus inoculation showed hyperresponsiveness to ACh. No airway hyperresponsiveness was noted in animals on day 1 or 9 post-virus exposure. Tracheal muscle rings were isolated from infected, thus hyperresponsive animals and the contractile force to ACh and KCl was examined in vitro, where their dose-response characteristics were similar to those of muscles from controls. CONCLUSION: The rat model for influenza virus-induced airway hyperreactivity was developed, which manifested a post-virus increase in airway responsiveness.

CD4+ T Helper Cells Engineered to Produce IL-10 Reverse Allergen-induced Airway Hyperreactivity and Inflammation / 소아알레르기및호흡기학회지

PURPOSE: Asthma is characterized by airway hyperreactivity to a variety of specific and nonspecific stimuli, by chronic airway inflammation with pulmonary eosinophilia, by mucus hypersecretion, and by increased serum IgE levels. T helper 2 (Th2) cells play a critical role in the pathogenesis of asthma, but the precise immunological mechanism that inhibit Th2 cell function in vivo are not well understood. METHODS: Using gene therapy, Th-cell lines were transferred intravenously into histocompatible SCID or OVA immunized BALB/c mice. Airway responsiveness was assessed by methacholine-induced airflow obstruction from conscious mice placed in a whole-body plethysmograph. Pulmonary airflow obstruction was measured by enhanced pause (Penh). RESULTS: We demonstrated that ovalbumin-specific (OVA-specific) Th cells engineered to express IL-10 abolished airway hyperreactivity induced by OVA-specific Th2 effector cells in SCID and BALB/c mice. The inhibitory effect of IL-10 transduced Th cells was antigen-specific and was reversed by neutralization of IL-10. CONCLUSION: Our results demonstrate that IL-10 transduced CD4+ Th cells in the respiratory mucosa can indeed regulate Th2-induced airway hyperreactivity.