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.

Eosinophil Development, Regulation of Eosinophil-Specific Genes, and Role of Eosinophils in the Pathogenesis of Asthma

Eosinophils arise from hematopoietic CD34+ stem cells in the bone marrow. They acquire IL-5Ralpha on their surface at a very early stage during eosinophilopoiesis, and differentiate under the strong influence of interleukin (IL)-5. They then exit to the bloodstream, and enter the lung upon exposure to airway inflammatory signals, including eotaxins. In inflamed tissues, eosinophils act as key mediators of terminal effector functions and innate immunity and in linking to adaptive immune responses. Transcription factors GATA-1, CCAAT/enhancer-binding protein, and PU.1 play instructive roles in eosinophil specification from multipotent stem cells through a network of cooperative and antagonistic interactions. Not surprisingly, the interplay of these transcription factors is instrumental in forming the regulatory circuit of expression of eosinophil-specific genes, encoding eosinophil major basic protein and neurotoxin, CC chemokine receptor 3 eotaxin receptor, and IL-5 receptor alpha. Interestingly, a common feature is that the critical cis-acting elements for these transcription factors are clustered in exon 1 and intron 1 of these genes rather than their promoters. Elucidation of the mechanism of eosinophil development and activation may lead to selective elimination of eosinophils in animals and human subjects. Furthermore, availability of a range of genetically modified mice lacking or overproducing eosinophil-specific genes will facilitate evaluation of the roles of eosinophils in the pathogenesis of asthma. This review summarizes eosinophil biology, focusing on development and regulation of eosinophil-specific genes, with a heavy emphasis on the causative link between eosinophils and pathological development of asthma using genetically modified mice as models of asthma.

Expression of eosinophil major basic protein and neutrophil elastase in nasal polyp tissue and secretion / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To explore the role in the pathogenesis of nasal polyp (NP) by comparison of eosinophil major basic protein (MBP), and neutrophil elastase (NE) in nasal polyps (NP) epithelium, stroma and the secretion of expression.@*METHOD@#Immunohistochemical detection of 30 cases of patients with chronic sinusitis (CRS) NP epithelium NE stroma and the expression and secretion of MBP.@*RESULT@#1. There were significant differences of the expression of NE and MBP in epithelial tissue, stroma and secretion compared with the control group (P 0.05), while there was significant difference between epithelial tissue and the secretion (P < 0.05); 3. There were significant differences of the average positive expression of MBP and NE among epithelial tissue, stroma and secretion (P < 0.05); 4. MBP and NE were usually degranulated in secretion, while usually located in eosinophils (Eos) and neutrophils (Neu) in epithelial and mesenchymal; 5. There were abundant expression of MBP and NE in epithelial shedding regional, while small amounts of expression in stroma and integrated epithelial; 6. Electron microscopy could show the characteristics of electron density of MBP and NE particles.@*CONCLUSION@#MBP and NE collaborated to cause pathological effects on the occurrence of NP.

Expression and its significance of eosinophil major basic protein in chronic rhinosinusitis / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To evaluate the expression of eosinophil major basic protein (MBP) in chronic rhinosinusitis (CRS) and discuss the role of MBP in the pathogenesis in CRS.@*METHOD@#Thirty-eight nasal mucus obtained from CRS patients were used to detect the expression of MBP by Elisa assay. Thirty nasal mucus samples from health people were used as control.@*RESULT@#The expression of MBP of nasal mucus obtained from CRS patients was obviously higher than that of nasal mucus obtained from control. There was significant statistical difference (P < 0.01).@*CONCLUSION@#MBP was involved in the formation of CRS.

Expression of eosinophil major basic protein mRNA in bronchial asthma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of eosinophil major basic protein (MBP) mRNA in bronchial asthma and explore its significance.</p><p><b>METHODS</b>Peripheral blood eosinophil MBP mRNA levels were measured in 40 patients with asthma and 20 normal controls by semi-quantitative RT-PCR. The association of MBP mRNA levels with eosinophil count and pulmonary function was also analyzed.</p><p><b>RESULTS</b>Compared with the normal control group, MBP mRNA level were significantly increased in asthma patients (0.37-/+0.11 vs 0.17-/+0.04, P<0.001), so was the eosinophil count (0.86-/+0.52 vs 0.21-/+0.10, P<0.001). MBP mRNA levels in patients with moderate persistent asthma (0.42-/+0.05) and those with severe persistent asthma (0.47-/+0.05) were significantly higher than those in patients with mild persistent asthma (0.25-/+0.06, P<0.001), and the difference in MBP mRNA levels between moderate persistent asthma patients and severe ones was also significant (P<0.05). Among the asthma patients, MBP mRNA levels showed an inverse correlation with pulmonary function (r=-0.7490, P<0.001).</p><p><b>CONCLUSION</b>Increased MBP mRNA expression level may correlate with the severity of asthma. MBP may play an important role in the development of asthma.</p>