title: Bacillus subtilis KCTC 11782BP-produced alginate oligosaccharide effectively suppresses asthma via T-helper cell type 2-related cytokines.
abstract: According to the World Health Organization in 2013, 235 million people are afflicted with asthma. Asthma is a severe pulmonary disease that can be caused by the imbalance of T-helper (Th) type 1 (Th1) and type 2 (Th2) cells, and it is potentially fatal. In this study, we evaluated the anti-asthmatic effect of alginate oligosaccharide (AO), which was prepared from seaweed and converted by Bacillus subtilis KCTC 11782BP, in the mouse model of ovalbumin (OVA)-induced asthma. BALB/c mice were divided into the vehicle control (sensitized but not challenged), asthma induction, positive control (1 mg/kg dexamethasone), 50 mg/kg/day AO-treated, 200 mg/kg/day AO-treated, and 400 mg/kg/day AO-treated groups. The numbers or levels of inflammatory cells, eosinophils, and immunoglobulin (Ig) E were measured in bronchoalveolar lavage fluid (BALF), and asthma-related morphological and cytokine changes were analyzed in lung tissues. Our results show that AO dramatically reduced inflammatory cell numbers, eosinophil count, and IgE levels in BALF, and it dose-dependently inhibited asthmatic histopathological changes in the lung. In addition, AO dose-dependently suppressed the expression of CD3+ T-cell co-receptors, CD4+ Th cells, CD8+ cytotoxic T-cell-related factors, macrophages, and MHCII class. AO dose-dependently decreased the expression levels of Th1/2 cells-regulatory transcription factors such as GATA-3 which modulates Th2 cell proliferation and T-bet which does Th1 cell proliferation. The mRNA levels of all Th1/2-related cytokines, except IL-12α, were dose-dependently suppressed by AO treatment. In particular, the mRNA levels of IL-5, IL-6, and IL-13 were significantly inhibited by AO treatment. Our findings suggest that AO has the potential to be an anti-asthmatic drug candidate, due to its modulation of Th1/Th2 cytokines, which contribute to the pathogenesis of asthma.
authors: Food Industry Development Team, Jeonnam Biofood Technology Center, Naju, Korea.
authors: Mi-Ae
authors: MA
authors: Bang
authors: Department of Oriental Medicine Materials, Dongshin University, Naju, Korea.
authors: Ji-Hye
authors: JH
authors: Seo
authors: Korea Institute of Toxicology, Daejeon, Korea.
authors: Joung-Wook
authors: JW
authors: Seo
authors: Research Institute of Bioscience and Biotechnology, Bioresource Inc., Naju, Korea.
authors: Gyung Hyun
authors: GH
authors: Jo
authors: Research Institute of Bioscience and Biotechnology, Bioresource Inc., Naju, Korea.
authors: Seoung Ki
authors: SK
authors: Jung
authors: College of Veterinary Medicine, Kyungpook National University, Daegu, Korea.
authors: Ri
authors: R
authors: Yu
authors: Department of Oriental Medicine Materials, Dongshin University, Naju, Korea.
authors: Dae-Hun
authors: DH
authors: Park
authors: College of Veterinary Medicine, Kyungpook National University, Daegu, Korea.
authors: Sang-Joon
authors: SJ
authors: Park
mesh_terms: D000464:Alginates / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D001412:Bacillus subtilis / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D020723:Glucuronic Acid / Q000494:pharmacology / Q000627:therapeutic use; D006603:Hexuronic Acids / Q000494:pharmacology / Q000627:therapeutic use; D007073:Immunoglobulin E / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D000464:Alginates; D018927:Anti-Asthmatic Agents; D016207:Cytokines; D006603:Hexuronic Acids; D007073:Immunoglobulin E; D020723:Glucuronic Acid