Novel glutathione-containing dry-yeast extracts inhibit eosinophilia and mucus overproduction in a murine model of asthma
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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.
Abstract
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.
참고문헌 (38)
- Holgate ST, "The sentinel role of the airway epithelium in asthma pathogenesis", Immunol Rev, 242, pp.205~219 (2011)
- Pelaia G, "Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma", Mediators Inflamm, 2015, pp.879783~ (2015)
- Possa SS, "Eosinophilic inflammation in allergic asthma", Front Pharmacol, 4, pp.46~ (2013)
- Ohashi Y, "Airway hyperresponsiveness, increased intracellular spaces of bronchial epithelium, and increased infiltration of eosinophils and lymphocytes in bronchial mucosa in asthma", Am Rev Respir Dis, 145, pp.1469~1476 (1992)
- Saitoh T, "Relationship between epithelial damage or basement membrane thickness and eosinophilic infiltration in nasal polyps with chronic rhinosinusitis", Rhinology, 47, pp.275~279 (2009)
- Pease JE, "Asthma, allergy and chemokines", Curr Drug Targets, 7, pp.3~12 (2006)
- Pope SM, "The eotaxin chemokines and CCR3 are fundamental regulators of allergen-induced pulmonary eosinophilia", J Immunol, 175, pp.5341~5350 (2005)
- Kew KM, "Increased versus stable doses of inhaled corticosteroids for exacerbations of chronic asthma in adults and children", Cochrane Database Syst Rev, pp.CD007524~ (2016)
- Kai M. Beeh, "The Role of Bronchodilators in Preventing Exacerbations of Chronic Obstructive Pulmonary Disease", Tuberculosis and Respiratory Diseases, 79(4), pp.241~247 (2016), 대한결핵및호흡기학회
- Papathanassiou E, "Severe asthma: anti-IgE or anti-IL-5?", Eur Clin Respir J, 3, pp.31813~ (2016)
- Patel TR, "IgE and eosinophils as therapeutic targets in asthma", Curr Opin Allergy Clin Immunol, 17, pp.42~49 (2017)
- Hosoki K, "Neutrophil recruitment by allergens contributes to allergic sensitization and allergic inflammation", Curr Opin Allergy Clin Immunol, 16, pp.45~50 (2016)
- Thomson NC, "Novel approaches to the management of noneosinophilic asthma", Ther Adv Respir Dis, 10, pp.211~234 (2016)
- Rose MC, "Airway mucus obstruction: Mucin glycoproteins, MUC gene regulation and goblet cell hyperplasia", Am J Respir Cell Mol Biol, 25, pp.533~537 (2001)
- Kim V, "Chronic bronchitis and chronic obstructive pulmonary disease", Am J Respir Crit Care Med, 187, pp.228~237 (2013)
- Boucherat O, "Cellular and molecular mechanisms of goblet cell metaplasia in the respiratory airways", Exp Lung Res, 39, pp.207~216 (2013)
- Lambrecht BN, "The airway epithelium in asthma", Nat Med, 18, pp.684~692 (2012)
- Lai H, "New pharmacotherapy for airway mucus hypersecretion in asthma and COPD: targeting intracellular signaling pathways", J Aerosol Med Pulm Drug Deliv, 23, pp.219~231 (2010)
- Takeyama K, "Role of epidermal growth factor receptor in maintaining airway goblet cell hyperplasia in rats sensitized to allergen", Clin Exp Allergy, 38, pp.857~865 (2008)
- Tanabe T, "Clarithromycin inhibits interleukin-13-induced goblet cell hyperplasia in human airway cells", Am J Respir Cell Mol Biol, 45, pp.1075~1083 (2011)
- Davis CW, "Regulated airway goblet cell mucin secretion", Annu Rev Physiol, 70, pp.487~512 (2008)
- Bruse S, "Increased methylation of lung cancer-associated genes in sputum DNA of former smokers with chronic mucous hypersecretion", Respir Res, 15, pp.2~ (2014)
- Lin CH, "Protective effects of the polyphenol sesamin on allergen-induced T(H)2 responses and airway inflammation in mice", PLoS One, 9, pp.e96091~ (2014)
- Gong JH, "Kaempferol suppresses eosionphil infiltration and airway inflammation in airway epithelial cells and in mice with allergic asthma", J Nutr, 142, pp.47~56 (2012)
- O'Donnell R, "Inflammatory cells in the airways in COPD", Thorax, 61, pp.448~454 (2006)
- Swaminathan GJ, "Eosinophil-granule major basic protein, a C-type lectin, binds heparin", Biochemistry, 44, pp.14152~14158 (2005)
- Cho IH, "Astragalin inhibits airway eotaxin-1 induction and epithelial apoptosis through modulating oxidative stress-responsive MAPK signaling", BMC Pulm Med, 14, pp.122~ (2014)
- Lee IT, "Role of NADPH oxidase", ROS in pro-inflammatory mediators-induced airway and pulmonary diseases, 2012, pp.84, 581~590
- Qu J, "Recent developments in the role of reactive oxygen species in allergic asthma", J Thorac Dis, 9, pp.E32~E43 (2017)
- Zuo L, "Molecular mechanisms of reactive oxygen species-related pulmonary inflammation and asthma", Mol Immunol, 56, pp.57~63 (2013)
- Pompella A, "The changing faces of glutathione, a cellular protagonist", Biochem Pharmacol, 66, pp.1499~1503 (2003)
- Wood LG, "Antioxidant and anti-inflammatory effects of resveratrol in airway disease", Antioxid Redox Signal, 13, pp.1535~1548 (2010)
- Shin D, "Dietary compound kaempferol inhibits airway thickening induced by allergic reaction in a bovine serum albumin-induced model of asthma", Int J Mol Sci, 16, pp.29980~29995 (2015)
- Hazlewood LC, "Dietary lycopene supplementation suppresses Th2 responses and lung eosinophilia in a mouse model of allergic asthma", J Nutr Biochem, 22, pp.95~100 (2011)
- Ashino S, "Janus kinase 1", 3 signaling pathways are key initiators of TH2differentiation and lung allergic responses, 2014, pp.133, 1162~1174
- Wijerathne CU, "Isoimperatorin attenuates airway inflammation and mucus hypersecretion in an ovalbumin-induced murine model of asthma", Int Immunopharmacol, 49, pp.67~76 (2017)
- Hao Y, "Pyocyanin-induced mucin production is associated with redox modification of FOXA2", Respir Res, 14, pp.82~ (2013)
- Jung JY, "Antioxidant and antiasthmatic effects of saucerneol D in a mouse model of airway inflammation", Int Immunopharmacol, 11, pp.698~705 (2011)
