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1.
Sheka Yagub Aloyouni Charis-Patricia Segeritz Ashley M. Sherrid Matthew J. Gold Daniela I. M. Loeffler Marie-Renée Blanchet Bing Cai Jeremy Hirota Kelly M. McNagny Tobias R. Kollmann 《Allergy, asthma & immunology research》2014,6(4):341-349
Purpose
Asthma is a chronic respiratory disorder that leads to inflammation and narrowing of the airways. Its global prevalence has attained epidemic levels and treatment options that reach beyond temporary relief of symptoms are urgently needed. Since the processes leading to clinically symptomatic asthma start early in life, we set out to systematically evaluate a neonatal immunotherapeutic based on Listeria monocytogenes (Lm) for the control of allergic sensitization.Methods
We modified Lm to express the model allergen, ovalbumin (OVA), and tested the ability of neonatal immunization with this strain to control allergic sensitization in a mouse model of OVA-induced asthma. Mice were immunized as newborns with live or heat killed LmOVA or live Lm, followed 6 weeks later by allergic sensitization with OVA. In order to determine whether the TH1-polarizing effect of this vaccine vector inadvertently may exacerbate development of certain TH1-driven allergic diseases, mice immunized as newborns were assessed in a model of adult hypersensitivity pneumonitis (HP).Results
Both LmOVA and Lm-control vaccines were highly effective in providing long-lasting protection from airway inflammation after only one immunization given perinatally. Serum antibody levels and lung cytokine production suggest that this prophylactic strategy is associated with an allergen specific TH1-dominated response. Specifically, LmOVA vaccinated mice displayed significantly elevated OVA-specific serum IgG2a, but no difference in anti-OVA IgE antibodies and only slightly decreased anti-OVA IgG1 antibodies. Importantly, Lm-based neonatal vaccination did not exacerbate Th1/Th17 driven HP, arguing against broad spectrum immune skewing.Conclusions
Our findings highlight the promise of early life Lm-based immunomodulatory interventions as a prophylactic strategy for allergic asthma. 相似文献2.
Young-Joon Kim Ha-Jung Kim Mi-Jin Kang Ho-Sung Yu Ju-Hee Seo Hyung-Young Kim Seoung-Ju Park Yong-Chul Lee Soo-Jong Hong 《Allergy, asthma & immunology research》2014,6(3):201-207
Purpose
Bacillus Calmette-Guérin (BCG) is known to suppress the asthmatic responses in a murine model of asthma and to induce dendritic cells (DCs) maturation. Mature DCs play a crucial role in the differentiation of regulatory T cells (Tregs), which are known to regulate allergic inflammatory responses. To investigate whether BCG regulates Tregs in a DCs-mediated manner, we analyzed in a murine model of asthma.Methods
BALB/c mice were injected intraperitoneally with BCG or intravenously with BCG-stimulated DCs and then sensitized and challenged with ovalbumin (OVA). Mice were analysed for bronchial hyperresponsiveness (BHR), the influx of inflammatory cells in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. To identify the mechanisms, IgE, IgG1 and IgG2a in the serum were analysed and the CD25+ Tregs in the mice were depleted with anti-CD25 monoclonal antibody (mAb).Results
BCG and the transfer of BCG-stimulated DCs both suppressed all aspects of the asthmatic responses, namely, BHR, the production of total IgE and OVA-specific IgE and IgGs, and pulmonary eosinophilic inflammation. Anti-CD25mAb treatment reversed these effects.Conclusions
BCG can attenuate the allergic inflammation in a mouse model of asthma by a Tregs-related mechanism that is mediated by DCs. 相似文献3.
Seong-Ok Jang Ha-Jung Kim Young-Joon Kim Mi-Jin Kang Ji-Won Kwon Ju-Hee Seo Hyung Young Kim Byoung-Ju Kim Jinho Yu Soo-Jong Hong 《Allergy, asthma & immunology research》2012,4(3):150-156
Purpose
Probiotic bacteria can induce immune regulation or immune tolerance in allergic diseases. The underlying mechanisms have been recently investigated, but are still unclear. The aim of this study was to evaluate the protective effects of the probiotic Lactobacillus rhamnosus (Lcr35) in a mouse model of asthma and to identify its mechanism of action.Methods
Lcr35 was administered daily by the oral route at a dosage of 1×109 CFU/mouse in BALB/c mice for 7 days before the first sensitization. Clinical parameters and regulatory T (Treg) cells were examined. The role of CD4+CD25+Foxp3+ Treg cells was analyzed using a Treg cell-depleting anti-CD25 monoclonal antibody (mAb).Results
Airway hyperresponsiveness, total IgE production, pulmonary eosinophilic inflammation, and splenic lymphocyte proliferation were suppressed after Lcr35 treatment. Th1 (IFN-γ) and Th2 (IL-4, IL-5, and IL-13) cytokines in the serum were suppressed, and the percentage of CD4+CD25+Foxp3+ Treg cells in the spleen was significantly increased in the Lcr35 treatment group. Anti-CD25 mAb administration abolished the protective effects of Lcr35, indicating that CD4+ CD25+Foxp3+ Treg cells are essential in mediating the activity of Lcr35.Conclusions
Oral administration of Lcr35 attenuated the features of allergic asthma in a mouse model and induced immune regulation by a CD4+CD25+Foxp3+ Treg cell-mediated mechanism. 相似文献4.
Tae-Hyoun Kim Yeong-Min Park Seung-Wook Ryu Dong-Jae Kim Jae-Hak Park Jong-Hwan Park 《Allergy, asthma & immunology research》2014,6(2):163-168
Purpose
Asthma is a pulmonary chronic inflammatory disease characterized by airway obstruction and hyperresponsiveness. Pattern recognition receptors are known to play a key role in the development of allergic diseases as well as host defenses against microbial infection. Receptor interacting protein 2 (RIP2), a serine/threonine kinase, is an adaptor molecule of NOD1 and NOD2, and genetic variation in this receptor is known to be associated with the severity of allergic asthma in children. In this study, we examined the role of RIP2 in the development of allergic airway inflammation in a mouse model.Methods
Airway inflammation was induced in mice through intranasal administration of ovalbumin (OVA) after 2 intraperitoneal immunizations with OVA. Lung inflammation and mucus hypersecretion were examined histologically and total cell infiltration in bronchoalveolar (BAL) fluids was determined. Levels of the Th2-related cytokines, IL-5 and IL-13, in lung extracts were measured by ELISA. Serum antigen-specific IgE and IgG1 levels were also assessed.Results
OVA-induced lung inflammation and mucus hypersecretion were not different between WT and RIP2-deficient mice. The IL-5 and IL-13 levels in the bronchoalveolar (BAL) fluids were also not impaired in RIP2-deficient mice compared to WT mice. Moreover, RIP2 deficiency did not affect serum OVA-specific IgG1 and IgE levels.Conclusions
Our results suggest that RIP2 is not associated with the development of allergic airway inflammation. 相似文献5.
Kyu-Young Oh Mi-Jin Kang Won-Ah Choi Ji-Won Kwon Byoung-Ju Kim Jinho Yu Soo-Jong Hong 《Allergy, asthma & immunology research》2010,2(2):127-133
Purpose
T cells play a central role in cell-mediated immunity, atopic disease, and asthma. The balance of CD28/cytotoxic T-lymphocyte antigen 4 (CTLA4)-derived signal transduction plays an important role in the activation of T cells and an increased immunoglobulin E (IgE) response. The aim of the current study was to investigate the association between polymorphisms in the genes encoding both CTLA4 and the high-affinity IgE receptor 1B (FCER1B) and serum IgE levels in Korean children with asthma.Methods
We enrolled 238 controls and 742 children with asthma. The CTLA4 +49A/G and FCER1B -654C/T polymorphisms were genotyped by PCR-restriction fragment length polymorphism analysis.Results
We observed no difference in the distribution of CTLA4 +49A/G among controls, children with asthma, and those with atopic asthma. In contrast, the GA genotype of CTLA4 +49A/G in children with atopic asthma was significantly higher compared to that in those with non-atopic asthma. Moreover, significantly higher log Dp/Df-specific IgE levels were found in children with asthma and those with atopic asthma carrying one or two copies of the CTLA4 +49A versus those homozygous for +49G. Gene-gene interactions between CTLA4 and FCER1B with the heterozygote and homozygote of variant genotypes were associated with the log Dp/Df-specific IgE levels, but not asthma development. In addition, children with Dp/Df (+) asthma carried an elevated combined genotype of risk allele compared to those with Dp/Df (-) asthma.Conclusions
The CTLA4 +49A/G polymorphism may contribute to the production of IgE in Korean children with asthma, especially in Dp/Df-specific IgE levels, but not in the direct development of asthma. In addition, Dp/Df-specific IgE levels with a FCER1B -654C/T polymorphism may involve additive effects. 相似文献6.
Myung Shin Kim Kyung-Ah Cho Young Joo Cho So-Youn Woo 《Allergy, asthma & immunology research》2013,5(4):197-206
Purpose
Asthma is a chronic inflammatory disease of the airways associated with structural changes and airway remodeling. Interleukin (IL)-9 has pleiotropic effects on both inflammatory cells and airway structural cells, which are involved in asthma pathogenesis. We evaluated the effects of IL-9 blockade on chronic airway inflammation.Methods
Acute airway inflammation was induced in Balb/c mice using aerosolized ovalbumin (OVA), whereas chronic asthma was induced by OVA exposure for 5 weeks with anti-IL-9 or isotype-matched antibody (Ab) treatment during the OVA challenge. Inflammatory cells in bronchoalveolar lavage fluid (BALF) were counted and lung tissues were stained to detect cellular infiltration, mucus deposition, and collagen accumulation. The levels of interferon (IFN)-γ, IL-4, IL-5, IL-9, IL-17, and immunoglobulin E (IgE) in BALF were measured using enzyme linked immunosorbent assays, and profiles of inflammatory cells and subsets of T helper (Th) cells were analyzed using flow cytometry.Results
IL-9, IL-17, and IFN-γ levels were significantly increased in the chronic group compared to the acute asthma group. However, the number of IL-9-positive cells was not affected, with a decrease in Th17 cells in OVA-challenged caspase-1 knockout mice. Numbers of eosinophils, neutrophils, B cells, mast cells, and Th17 cells decreased after administration of anti-IL-9 Ab. Total IgE, IL-5, IL-9, and IL-17 levels were also lower in the anti-IL-9 group.Conclusions
Our results suggest that anti-IL-9 Ab treatment inhibits pulmonary infiltration of inflammatory cells and cytokine production, especially IL-17. These results provide a basis for the use of an anti-IL-9 Ab to combat IL-17-mediated airway inflammation. 相似文献7.
Kyoung Yong Jeong June Yong Lee Mina Son Myung-hee Yi Tai-Soon Yong Jung U Shin Kwang Hoon Lee Yoon-Ju Kim Kyung Hee Park Hye Jung Park Jae-Hyun Lee Jung-Won Park 《Allergy, asthma & immunology research》2015,7(5):483-488
Purpose
Measurement of IgE specific to purified house dust mite (HDM) allergens may improve allergy diagnosis. This study aimed to investigate the sensitization profiles of Korean HDM allergic subjects suffering from respiratory allergy and atopic dermatitis (AD) to Der f 1, Der f 2, Der f 6, Der f 8, Der f 10, and Der f 20.Methods
Recombinant HDM allergens were produced in Pichia pastoris (Der f 1) or Escherichia coli (5 allergens). IgE reactivity to the individual recombinant allergens and total extract of mite was assessed by ELISA.Results
Der f 1 was recognized by 79.1%, Der f 2 by 79.1%, Der f 6 by 9.3%, Der f 8 by 6.2%, Der f 10 by 6.2%, and Der f 20 by 6.6% of the patients'' sera tested, while the prevalence of IgE reactivity to total mite extract was 94.7%. Combination of Der f 1 and Der f 2 had a sensitivity of 87.6%. Specific IgE to Der f 2 alone was detected from 89.4% of HDM-sensitized respiratory allergy subjects and 92.3% to the combination of the 2 major allergens Der f 1 and Der f 2. However, sera from fewer patients with AD, namely 72.4% and 71.0%, recognized Der f 1 and Der f 2, respectively. The combination of 2 major allergens allowed diagnosis of 84.5% of the AD patients. No correlation between sensitization to specific allergens and HDM allergy entity was found.Conclusions
Der f 2 was the most frequently sensitized allergen among the HDM-sensitized respiratory and AD patients in Korea, and the combination of the group 1 and 2 major allergens increased the diagnostic sensitivity. Minor allergens did not significantly improve diagnostic sensitivity. However, further studies are needed to analyze the relationship between sensitization to other HDM allergens and the disease entity of the HDM allergy. 相似文献8.
Chan-Sun Park Tae-Bum Kim Keun Ae Moon Yun-Jeong Bae Hee Ran Lee Min Kyoung Jang Hee-Bom Moon You Sook Cho 《Allergy, asthma & immunology research》2010,2(1):41-47
Purpose
Chlamydophila pneumoniae infection in the airways is thought to be associated with the pathogenesis of asthma, especially in non-atopic severe asthma with irreversible airway obstruction that may be related to airway remodeling. Here, we investigated whether C. pneumoniae infection enhances the secretion of critical chemical mediators for airway remodeling, such as VEGF, TGF-β, and TIMP-1, in human bronchial epithelial cells (BECs) in a Th2-dominant microenvironment.Methods
Human bronchial epithelial cells (BEAS-2B cells) were infected with C. pneumoniae strain TW183 and cultured in both a Th1-dominant microenvironment with INF-γ and a Th2-dominant microenvironment with IL-4 or IL-13 added to the culture medium. The VEGF, TGF-β, and TIMP-1 levels in the culture supernatants were measured using enzyme-linked immunosorbent assays (ELISA). The activation of NF-κB in each experimental condition was determined using an electrophoretic mobility shift assay.Results
Chlamydophila pneumoniae-infected BECs showed enhanced secretion of VEGF, TGF-β, and TIMP-1 compared with non-infected BECs. The levels of cytokines secreted from BECs were increased more when IL-13 was added to the culture medium. C. pneumoniae-infected BECs also showed increased NF-κB activation.Conclusions
These results suggest that C. pneumoniae plays a role in the pathogenesis of airway remodeling in asthma, revealing a Th2-dominant immune response. Further studies are required to clarify the precise mechanism of C. pneumoniae infection in airway remodeling. 相似文献9.
Ye YM Kang YM Kim SH Lee HY Kim CW Park CS Hong CS Park HS 《Allergy, asthma & immunology research》2010,2(4):260-266
Purpose
A genetic polymorphism of the beta 2-adrenergic receptor is a major factor associated with the asthmatic phenotype. The association of this polymorphism with toluene diisocyanate (TDI)-induced asthma has not been investigated. We examined 103 TDI-induced asthma patients (TDI-OA), 60 asymptomatic exposed controls (AEC), and 263 unexposed healthy controls (NC) in order to identify beta 2-adrenergic receptor gene (ADRB2) polymorphisms and the possible association with TDI-induced asthma.Methods
Single nucleotide polymorphisms (SNPs) of ADRB2 were genotyped by direct sequencing. Serum-specific IgE and IgG levels were measured using an enzyme-linked immunosorbent assay. Phenotypes and clinical patient parameters were compared.Results
SNPs were identified (-47 T>C, -20 T>C, Arg16Gly A>G, Gln27Glu C>G, Leu134Leu G>A, Arg175Arg C>A) during ADRB2 screening (from -231 to 793 bp). No significant differences in allelic and genotypic frequencies were noted for any of the six ADRB2 SNPs. The Arg16Gly A>G, Leu134Leu G>A, and Arg175Arg C>A SNPs and haplotype 1 [TTACGC] were significantly associated with specific IgE antibodies to the TDI-human serum albumin (HSA) conjugate in TDI-exposed subjects (P<0.05). Exposed workers with the ADRB2 ht1/ht1 homozygote had a significantly higher TDI-HSA conjugate-specific IgE sensitization rate than did those with the null ht1 haplotype (odds ratio, 15.40; 95% confidence interval, 1.81-131.06).Conclusions
ADRB2 polymorphisms may affect IgE-specific sensitization to TDI-HSA conjugate in TDI-exposed workers. 相似文献10.
Jae-Uoong Shim Joon-Haeng Rhee Young-Il Koh 《Allergy, asthma & immunology research》2012,4(5):295-304
Purpose
Invariant natural killer T (iNKT) cells may play an important role in the pathogenesis of asthma in mice and humans. Thus, an agent that modulates the function of iNKT cells may have therapeutic potential to control asthma. We hypothesized that lipopolysaccharide (LPS)-, flagellin-, or CpG-induced changes in the cytokine milieu may modify and even inhibit the function of airway iNKT cells in asthma.Methods
Because increased α-galactosylceramide (GalCer)-induced airway hyperreactivity (AHR) reflects the presence of airway iNKT cells, α-GalCer-induced AHR, as well as inflammatory cells and cytokines in bronchoalveolar lavage (BAL) fluid, were determined 24 hours after in vivo treatment with LPS, flagellin, or CpG in naïve BALB/c mice. Intracellular IL-4 and IFN-γ were measured in spleen iNKT cells after in vitro treatment with LPS, flagellin, or CpG. A role for IL-12 following the treatments was determined.Results
Intranasal administration of LPS, flagellin, or CpG reduced development of α-GalCer-induced AHR, eosinophilic airway inflammation, and Th1 and Th2 cytokine responses in BAL fluid, while producing IL-12 in BAL fluid. Intraperitoneal administration of IL-12 mAb blocked the suppressive effect of LPS, flagellin, or CpG. In vitro treatment with LPS, flagellin, or CpG reduced production of IL-4 and IFN-γ from α-GalCer-stimulated spleen iNKT cells; these effects were ameliorated by addition of anti-IL-12 mAb.Conclusions
TLR4, 5, and 9 agonists may suppress the function of airway and spleen iNKT cells via IL-12-dependent mechanisms. Anergy of iNKT cells by IL-12 might play a role in suppression by these TLR agonists. 相似文献11.
Sun Hee Jung Jang-Mi Kwon Jae Won Shim Deok Soo Kim Hye Lim Jung Moon Soo Park Soo-Hee Park Jinmi Lee Won-Young Lee Jung Yeon Shim 《Yonsei medical journal》2013,54(6):1430-1437
Purpose
Obesity has been suggested to be linked to asthma. However, it is not yet known whether obesity directly leads to airway hyperreactivity (AHR) or obesity-induced airway inflammation associated with asthma. We investigated obesity-related changes in adipokines, AHR, and lung inflammation in a murine model of asthma and obesity.Materials and Methods
We developed mouse models of chronic asthma via ovalbumin (OVA)-challenge and of obesity by feeding a high-fat diet, and then performed the methacholine bronchial provocation test, and real-time PCR for leptin, leptin receptor, adiponectin, adiponectin receptor (adipor1 and 2), vascular endothelial growth factor (VEGF), transforming growth factor (TGF) β, and tumor necrosis factor (TNF) α in lung tissue. We also measured cell counts in bronchoalveolar lavage fluid.Results
Both obese and lean mice chronically exposed to OVA developed eosinophilic lung inflammation and AHR to methacholine. However, obese mice without OVA challenge did not develop AHR or eosinophilic inflammation in lung tissue. In obese mice, lung mRNA expressions of leptin, leptin receptor, VEGF, TGF, and TNF were enhanced, and adipor1 and 2 expressions were decreased compared to mice in the control group. On the other hand, there were no differences between obese mice with or without OVA challenge.Conclusion
Diet-induced mild obesity may not augment AHR or eosinophilic lung inflammation in asthma. 相似文献12.
Wangjian Zha Mei Su Mao Huang Jiankang Cai Qiang Du 《Allergy, asthma & immunology research》2016,8(2):161-169
Purpose
Pigment epithelium-derived factor (PEDF) is a recently discovered antiangiogenesis protein. PEDF possesses powerful anti-inflammatory, antioxidative, antiangiogenic, and antifibrosis properties. It has been reported that PEDF can regulate vascular endothelial growth factor (VEGF) expression. This study aimed to evaluate whether recombinant PEDF protein could attenuate allergic airway inflammation and airway remodeling via the negative regulation of VEGF using a murine model of chronic ovalbumin (OVA)-induced asthma and BEAS-2B human bronchial epithelial cells.Methods
In an in vivo experiment, mice sensitized with OVA were chronically airway challenged with aerosolized 1% OVA solution for 8 weeks. Treated mice were given injections of recombinant PEDF protein (50 or 100 µg/kg body weight) via the tail vein. In an in vitro experiment, we investigated the effects of recombinant PEDF protein on VEGF release levels in BEAS-2B cells stimulated with IL-1β.Results
Recombinant PEDF protein significantly inhibited eosinophilic airway inflammation, airway hyperresponsiveness, and airway remodeling, including goblet cell hyperplasia, subepithelial collagen deposition, and airway smooth muscle hypertrophy. In addition, recombinant PEDF protein suppressed the enhanced expression of VEGF protein in lung tissue and bronchoalveolar lavage fluid (BALF) in OVA-challenged chronically allergic mice. In the in vitro experiment, VEGF expression was increased after IL-1β stimulation. Pretreatment with 50 and 100 ng/mL of recombinant PEDF protein significantly attenuated the increase in VEGF release levels in a concentration-dependent manner in BEAS-2B cells stimulated by IL-1β.Conclusions
These results suggest that recombinant PEDF protein may abolish the development of characteristic features of chronic allergic asthma via VEGF suppression, providing a potential treatment option for chronic airway inflammation diseases such as asthma. 相似文献13.
Jae Woo Jung Jae Chol Choi Jong Wook Shin Jae Yeol Kim In Won Park Byoung Whui Choi 《Allergy, asthma & immunology research》2010,2(2):102-107
Purpose
Allergic sensitization is a risk factor for the development of bronchial asthma. This study was conducted to investigate clinical manifestations according to sensitized allergens in adult Korean patients with bronchial asthma.Methods
In total, 523 adult patients who were diagnosed with bronchial asthma between March 2002 and March 2008 were included in the study. All patients underwent skin prick tests for approximately 45 allergens or a specific IgE test. Sensitized allergens were grouped into the following categories: house dust mites, fungus, pollen, and animal dander. Atopy was defined as a positive skin prick test response or the presence of a specific IgE to one or more allergens.Results
Of the 523 patients, 295 (56%) were sensitized to one or more allergens. A younger median age, greater proportion of males, higher eosinophil counts, and higher total IgE levels were observed in the atopic asthma group compared to the non-atopic asthma group. The PC20 value was negatively correlated with eosinophil counts and total IgE in the atopic asthma group. In the subgroup analysis, patients sensitized to Cladosporium showed poorer pulmonary function and a higher response to bronchodilators. In addition, patients sensitized to Alternaria showed severer bronchial hyperresponsiveness than non-atopic patients with asthma. Finally, a gradual increase in the number of sensitized allergens was noted with increasing age, eosinophil counts, and total IgE levels.Conclusions
We suggest the need for identifying the existence of atopy and exact offending allergens at the time of asthma diagnosis, since significant differences in sex, age, blood test results, and lung function were observed according to atopy and sensitized allergens. 相似文献14.
Chian-Jiun Liou Pei-Yun Cheng Wen-Chung Huang Cheng-Chi Chan Meng-Chun Chen Ming-Ling Kuo Jiann-Jong Shen 《Allergy, asthma & immunology research》2014,6(6):548-557
Purpose
Lovastatin is an effective inhibitor of cholesterol synthesis. A previous study demonstrated that lovastatin can also suppress airway hyperresponsiveness (AHR) in murine model of asthma. We aimed to investigate the effect of lovastatin on mucus secretion and inflammation-associated gene expression in the lungs of murine model of asthma.Methods
Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) by intraperitoneal injection, and orally administered lovastatin from days 14 to 27 post-injection. Gene expression in lung tissues was analyzed using real-time polymerase chain reaction. AHR and goblet cell hyperplasia were also examined. BEAS-2B human bronchial epithelial cells were used to evaluate the effect of lovastatin on the expression of cell adhesion molecules, chemokines, and proinflammatory cytokines in vitro.Results
We showed that lovastatin inhibits the expression of Th2-associated genes, including eotaxins and adhesion molecules, in the lungs of murine model of asthma. Mucin 5AC expression, eosinophil infiltration and goblet cell hyperplasia were significantly decreased in the lung tissue of murine model of asthma treated with lovastatin. Furthermore, lovastatin inhibited AHR and expression of Th2-associated cytokines in bronchoalveolar lavage fluid. However, a high dose (40 mg/kg) of lovastatin was required to decrease specific IgE to OVA levels in serum, and suppress the expression of Th2-associated cytokines in splenocytes. Activated BEAS-2B cells treated with lovastatin exhibited reduced IL-6, eotaxins (CCL11 and CCL24), and intercellular adhesion molecule-1 protein expression. Consistent with this, lovastatin also suppressed the ability of HL-60 cells to adhere to inflammatory BEAS-2B cells.Conclusions
These data suggest that lovastatin suppresses mucus secretion and airway inflammation by inhibiting the production of eotaxins and Th2 cytokines in murine model of asthma. 相似文献15.
Lee SH Jang AS Kwon JH Park SK Won JH Park CS 《Allergy, asthma & immunology research》2011,3(3):205-211
Purpose
Severe asthma is characterized by high medication requirements to maintain good disease control or by persistent symptoms despite high medication use. The transfer of bone marrow-derived mesenchymal stem cells (BMDMSCs) to the injured lungs is a possible treatment for severe asthma. This study investigated the therapeutic effects of BMDMSCs in airway remodeling and inflammation in an experimental toluene diisocyanate (TDI)-induced asthma animal model of severe asthma.Methods
BMDMSCs were transferred into rats after TDI inhalation. Bronchoalveolar lavage (BAL) cell profiles, histological changes including an inflammatory index and goblet cell hyperplasia, and the airway response to methacholine using plethysmography were analyzed. Smooth muscle actin (SMA) and proliferating cell nuclear antigen (PCNA) protein expression were observed in lung tissue using immunohistochemical staining. The collagen content was measured in lung tissue sections and lung extracts using Masson''s trichrome staining and an immunoassay kit.Results
The numbers of inflammatory cells in BAL fluid, histological inflammatory index, airway response to methacholine, number of goblet cells, and amount of collagen were increased in TDI-treated rats compared with sham rats (P=0.05-0.002). BMDMSC transfer significantly reduced the TDI-induced increase in the inflammatory index and numbers of eosinophils and neutrophils in BAL fluid to levels seen in sham-treated rats (P<0.05). BMDMSC transfer significantly reduced the number of goblet cells, collagen deposition, and immune staining for SMA and PCNA with concomitant normalization of the airway response to methacholine.Conclusions
The systemic transfer of BMDMSCs effectively reduced experimental TDI-induced airway inflammation and remodeling and airway hyperreactivity. 相似文献16.
Jason Yongha Kim Jeong-Hyun Kim Byung-Lae Park Charisse Flerida A. Pasaje Joon Seol Bae Jong Sook Park An-Soo Jang Soo-Taek Uh Yong-Hoon Kim Mi-Kyeong Kim Inseon S. Choi Sang Heon Cho Byoung Whui Choi Choon-Sik Park Hyoung Doo Shin 《Allergy, asthma & immunology research》2013,5(1):34-41
Purpose
Aspirin exacerbated respiratory disease (AERD) results in a severe asthma attack after aspirin ingestion in asthmatics. The filamin A interacting protein 1 (FILIP1) may play a crucial role in AERD pathogenesis by mediating T cell activation and membrane rearrangement. We investigated the association of FILIP1 variations with AERD and the fall rate of forced expiratory volume in one second (FEV1).Methods
A total of 34 common FILIP1 single nucleotide polymorphisms (SNPs) were genotyped in 592 Korean asthmatic subjects that included 163 AERD patients and 429 aspirin-tolerant asthma (ATA) controls.Results
This study found that 5 SNPs (P=0.006-0.01) and 2 haplotypes (P=0.01-0.03) of FILIP1 showed nominal signals; however, corrections for the multiple testing revealed no significant associations with the development of AERD (Pcorr>0.05). In addition, association analysis of the genetic variants with the fall rate of FEV1, an important diagnostic marker of AERD, revealed no significant evidence (Pcorr>0.05).Conclusions
Although further replications and functional evaluations are needed, our preliminary findings suggest that genetic variants of FILIP1 might be not associated with the onset of AERD. 相似文献17.
Purpose
Recent studies have reported that Asian sand dust (ASD) has a potential risk of aggravating airway inflammation. The purpose of this study was to investigate the effect of ASD on inflammation and mucin production in the airways of allergic mice.Methods
Forty BALB/c female mice were divided into four groups: saline (group 1); ASD (group 2); ovalbumin (OVA) alone (group 3); and OVA+ASD (group 4). OVA-specific immunoglobulin E (IgE) in serum and interleukin (IL)-4, IL-5, IL-13, and interferon-gamma (IFN-γ) in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Hematoxylin & eosin (H&E) and Periodic acid-Schiff (PAS) staining was performed on lung tissues. In addition, immunohistochemical staining for IL-4, IL-5, MUC5AC, and transforming growth factor alpha (TGF-α) was conducted.Results
Serum IgE levels were significantly higher in group 4 than in group 3 (P<0.05). IL-4 and IL-5 in BALF were significantly higher in group 4 than in group 3 (P<0.05, respectively). Based on H&E staining, inflammatory cell numbers were significantly greater in group 4 than in the other groups (P<0.05). The number of PAS-positive cells was also significantly greater in groups 3 and 4 than in groups 1 and 2 (P<0.05). The numbers of IL-4 and IL-5-positive cells were higher in group 4 than in group 3 (P<0.05). The number of MUC5AC and TGF-α-positive cells were also higher in group 4 than in group 3 (P<0.05).Conclusions
Our data suggest that ASD increases cytokine expression and mucin production in an allergic murine model. The increased inflammatory reactions were related to cytokine production. 相似文献18.
Kyung Eun Lee Beom Ku Han Jae Yong Han Jung Yeon Hong Mi Na Kim Won Il Heo Myung Hyun Sohn Kyung Won Kim Kyu Earn Kim 《Yonsei medical journal》2014,55(4):999-1004
Purpose
House dust mites (HDMs) are an important source of indoor allergens associated with asthma, rhinitis and atopic dermatitis. Chicken immunoglobulin (Ig) Y is known to be a good alternative to mice and rabbit antibody production. In this study, we produced IgYs specific to HDMs and investigated their IgE immunoreactivities.Materials and Methods
Total IgYs were isolated from the yolks of White Leghorn hens immunized with either Dermatophagoides pteronyssinus or D. farinae protein extract. Control antibodies were separated from the yolks of immunized hens with phosphate buffered saline. IgYs specific to HDMs were analyzed using enzyme-linked immunosorbent assay and Western blotting analysis.Results
The concentration of egg IgY specific to D. farinae in an immunized hen increased and the highest achieved was 661.3 ug/mg (per an egg) on day 47, compared with 760 ug/mg IgY specific to D. pteronyssinus on day 16. The D. pteronyssinus or D. farinae-specific IgY was detected by binding of each mite proteins, and their immunoreactivities were elevated dependent of the specific IgY concentration.Conclusion
IgY specific to HDMs may be a promising antibody for immunological diagnosis as well as identification of possible resistance relating to HDM allergy. 相似文献19.
Eui-Ryoung Han Inseon S. Choi Han-Gyu Choi Hwa-Jung Kim 《Allergy, asthma & immunology research》2012,4(4):214-221
Purpose
Live/killed mycobacteria and culture supernatants can suppress asthmatic reactions. This study investigated whether mycobacterial secretory proteins have therapeutic effects on asthma.Methods
Mycobacterium bovis bacille Calmette-Guérin (BCG; 2×105 CFUs) and mycobacterial secretory proteins (Ag85 complex, 38-kDa protein or MPB70; 4 or 20 µg) were administered intraperitoneally to female BALB/c mice with established airway hyperresponsiveness. One week after treatment, the mice underwent a methacholine challenge test, and then inflammatory cell numbers in bronchoalveolar lavage fluid (BAL) and around bronchi (<500 µm), and cytokine levels in splenocyte supernatants, were assessed.Results
BCG and all of the tested secretory proteins significantly improved airway sensitivity compared to baseline values (P<0.05). The secretory protein Ag85 complex significantly suppressed airway reactivity also (P<0.05), while 38-kDa protein significantly suppressed reactivity and maximal narrowing (P<0.05). The number of eosinophils in BAL and around bronchi, and the goblet cell proportion, were also significantly reduced in mice in both the BCG and secretory protein groups compared to the asthma control group. IFN-γ/IL-5 ratios were significantly higher in mice treated with BCG, 4 µg MPB70 or 4 µg 38-kDa protein than in asthma control mice (P<0.05), and were negatively associated with airway hyperresponsiveness, peribronchial eosinophil numbers and goblet cell proportion (all P<0.05). IL-17A was positively correlated with IL-5 (r=0.379, P<0.001), maximal airway narrowing, peribronchial eosinophil numbers and goblet cell proportion (all P<0.05).Conclusions
Secretory proteins from BCG and M. tuberculosis and live BCG were effective against established asthma, their effects being accompanied by increased IFN-γ/IL-5 ratios. Thus, allergic asthma could be effectively treated with mycobacterial secretory proteins. 相似文献20.
An-Soo Jang Jong-Sook Park June-Hyuk Lee Sung-Woo Park Do-Jin Kim Soo-Taek Uh Young-Hoon Kim Choon-Sik Park 《Allergy, asthma & immunology research》2010,2(2):108-113