Novel glutathione-containing dry-yeast extracts inhibit eosinophilia and mucus overproduction in a murine model of asthma

BACKGROUND/OBSECTIVE: Airway inflammation by eosinophils, neutrophils and alveolar macrophages is a characteristic feature of asthma that leads to pathological subepithelial thickening and remodeling. Our previous study showed that oxidative stress in airways resulted in eosinophilia and epithelial apoptosis. The current study investigated whether glutathione-containing dry yeast extract (dry-YE) ameliorated eosinophilia, goblet cell hyperplasia and mucus overproduction. MATERIALS/METHOD: This study employed 2 µg/mL lipopolysaccharide (LPS)- or 20 ng/mL eotaxin-1-exposed human bronchial epithelial cells and ovalbumin (OVA)-challenged mice. Dry-YE employed in this study contained a significant amount of glutathione (140 mg in 100 g dry yeast). RESULTS: Human bronchial epithelial cell eotaxin-1 and mucin 5AC (MUC5AC) were markedly induced by the endotoxin LPS, which was dose-dependently attenuated by nontoxic dry-YE at 10-50 µg/mL. Moreover, dry-YE inhibited the MUC5AC induction enhanced by eotaxin-1, indicating that eotaxin-1-mediated eosinophilia may prompt the MUC5AC induction. Oral supplementation with 10-100 mg/kg dry-YE inhibited inflammatory cell accumulation in airway subepithelial regions with a reduction of lung tissue level of intracellular adhesion molecule-1. In addition, ≥ 50 mg/kg dry-YE diminished the lung tissue levels of eotaxin-1, eosinophil major basic protein and MUC5AC in OVA-exposed mice. Alcian blue/periodic acid schiff staining revealed that the dry-YE supplementation inhibited goblet cell hyperplasia and mucus overproduction in the trachea and bronchiolar airways of OVA-challenged mice. CONCLUSIONS: Oxidative stress may be involved in the induction of eotaxin-1 and MUC5AC by endotoxin episode and OVA challenge. Dry-YE effectively ameliorated oxidative stress-responsive epithelial eosinophilia and mucus-secreting goblet cell hyperplasia in cellular and murine models of asthma.

Allergic Rhinitis in Preschool Children and the Clinical Utility of FeNO

PURPOSE: The nature of allergic rhinitis (AR) in preschool aged children remains incompletely characterized. This study aimed to investigate the prevalence of AR and its associated risk factors in preschool-aged children and to assess the clinical utility of fractional exhaled nitric oxide (FeNO). METHODS: This general population-based, cross-sectional survey included 933 preschool-aged (3- to 7-year-old) children from Korea. Current AR was defined as having nasal symptoms within the last 12 months and physician-diagnosed AR. RESULTS: The prevalence of current AR in preschool children was 17.0% (156/919). Mold exposure (adjusted odds ratio [aOR], 1.67; 95% confidence interval [CI], 1.15-2.43) and the use of antibiotics (aOR, 1.97; 95% CI, 1.33-2.90) during infancy were associated with an increased risk of current AR, whereas having an older sibling (aOR, 0.52; 95% CI, 0.35-0.75) reduced the risk. Children with current atopic AR had significantly higher geometric mean levels of FeNO compared to those with non-atopic rhinitis (12.43; range of 1standard deviation [SD], 7.31-21.14 vs 8.25; range of 1SD, 5.62-12.10, P=0.001) or non-atopic healthy children (8.58; range of 1SD, 5.51-13.38, P<0.001). The FeNO levels were higher in children with current atopic AR compared with atopic healthy children (9.78; range of 1SD, 5.97-16.02, P=0.083). CONCLUSIONS: Mold exposure and use of antibiotics during infancy increases the risk of current AR, whereas having an older sibling reduces it. Children with current atopic AR exhibit higher levels of FeNO compared with non-atopic rhinitis cases, suggesting that FeNO levels may be a useful discriminatory marker for subtypes of AR in preschool children.

Risk factors, lung function and bronchial hyperresponsiveness in current dust mite-induced allergic rhinitis

PURPOSE: We analyzed the pulmonary function and risk factors of allergic rhinitis (AR) in dust mite-sensitized children with current AR and no history of asthma. METHODS: In this cross-sectional study, demographic and disease-related information was obtained from 1,792 Korean children aged 9-12 years using a questionnaire, skin-prick testing, spirometric analysis, and methacholine challenge testing. RESULTS: A total of 672 children were analyzed. The control group consisted of 583 children without any allergic diseases who were not sensitized to 16 common allergens. The group with current AR and dust mite sensitization consisted of 89 children. Binary logistic regression analysis showed that helminth infection (adjusted odds ratio [aOR], 2.88; 95% confidence interval [CI], 1.23-6.77) and antibiotic use during infancy (aOR, 1.89; 95% CI, 1.10-3.25) were the risk factors. Pet ownership (aOR, 0.32; 95% CI, 0.15-0.69) and older siblings (aOR, 0.58; 95% CI, 0.35-0.96) were protective factors. Spirometry results did not differ between the control and dust mite-induced AR groups. None of the children showed a bronchodilator response. However, 8.5%, 7.1%, and 2.1% of the control-group children and 28.7%, 23.0%, and 8.0% of the dust mite-induced AR-group children showed methacholine PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second) values of < or =25 mg/mL, < or =16 mg/mL, and < or =8 mg/mL, respectively (P<0.01). CONCLUSION: The prevalence of current dust mite-induced AR may be reduced by controlling environmental factors. Even though the spirometry results seemed to be normal, bronchial hyperresponsiveness occurred more frequently in children with dust mite-induced AR than in normal children.

Effect of Erythromycin on Pro-inflammatory Signalings by Particles

Purpose: In periprosthetic osteolysis, cytokines, which are secreted from macrophages by the stimulation of particles, up-regulate the signaling for osteoclast activation through RANKL (Receptor activator of Nuclear Factor Kappa-B Ligand). This study compared the reaction to the particles and RANKL in the macrophages by examining the changes in the pro-inflammatory signals. In addition, because erythromycin has an anti-inflammatory effect, the effect of erythromycin on the pro-inflammatory signals by particles and RANKL was also analyzed to clarify the mechanism for the anti-resorptive effect with particles. Materials and Methods: The Raw 264.7 cell line (murine macrophage cell line) was used for these experiments. The particles were made from PMMA (poly-methyl-meth-acrylate) and UHMWPE (ultra high molecular weight polyethylene) to enhance their stimulatory effects. Under the same culture conditions used for macrophages, the cells were treated with either particles or RANKL. The differences in the production of TNF-α, activities of MAP kinase, I-κB and reactive oxygen species (ROS) between the particle and RANKL treated macrophages were examined. The influence of erythromycin on these models was also observed. Results: Erythromycin inhibited ERK and p38 phosphorylation in both models, and suppressed the increase in H2O2 production in the particle-treated macrophages. However, erythromycin inhibited neither the production of TNF- in both models nor the production of H2O2 in the RANKL-treated macrophages. In addition, erythromycin reversed the suppression of I-κB by the particles. Conclusion: For the response of macrophages, erythromycin mainly suppresses the particle induced ROS and NF-κB activation compared with RANKL-induced osteoclastogenesis signaling. Erythromycin might suppress particle-induced osteolysis through these anti-inflammatory effects. Therefore, further studies on the downstream signals of osteoclastogenesis will be needed.

Antioxidative Effects of Water-Soluble Chitinous Compounds on Oxidation of Low Density Lipoprotein in Macrophages

It has been proposed that oxidative modification of LDL (oxLDL) plays a significant role in the pathogenicity of atherogenesis. We tested the hypothesis that chitin and chitosan may function as antioxidants with respect to 0.1 mg cholesterol/ml LDL incubated with 5 micrometer Cu2+ alone or in the P338Dl mouse macrophage system using L-ascorbic acid as a standard classical antioxidant. The degree of oxLDL formation was ascertained by the relative electrophoretic mobility (rEM) in the combination of thiobarbituric acid reactive substances (TBARS) levels, and the cytotoxicity of oxLDL was detected by macrophage viability. The oxLDL uptake and foam cell formation of macrophages were measured by Oil Red O staining. Incubation with Cu2+ and macrophages increased rEM of LDL and stimulated TBARS formation. Culture of macrophages with LDL in the presence 5 micrometer Cu2+ induced macrophage death. In cell-free system 200 microgram/ml water-soluble chitosan and chitosan-oligosaccharide blocked oxLDL formation. Water-soluble chitosan and chitosan-oligosaccharide blocked oxLDL formation near-completely relative to L-ascorbic acid, whereas water-soluble chitin and chitin-oligosaccharide had no measurable antioxidant effect. In macrophage system water-soluble chitosan and chitosan-oligosaccharide blocked oxidation of LDL with a significant increase in cell viability, and decreased TBARS in medium. As for the inhibitory effect on macrophage foam cell formation, chitosan and its oligosaccharide, but not watersoluble chitin, revealed the effectiveness. The endothelial expression of lectin-like oxLDL receptor-1 (LOX-1) was tested by Western blot analysis, and chitosan, chitosan-oligosaccharide and chitin-oligosaccharide blocked LOX-1 expression. These results indicate that water-soluble chitosan and its oligosaccharide showed the inhibitory effect on Cu2+-induced LDL oxidation of macrophages, and chitosan, chitosan-oligosaccharide and chitin-oligosaccharide had blocking effect on oxLDL receptor expression in the human umbilical vein endothelial system. Thus, water-soluble chitosan and its oligosaccharides possess anti-atherogenic potentials possibly through the inhibition of macrophage LDL oxidation or endothelial oxLDL receptor expression depending on chemical types.l types.