title: Inflammation-induced expression of the alarmin interleukin 33 can be suppressed by galacto-oligosaccharides.
abstract: BACKGROUND
  The alarmin interleukin 33 (IL-33) and its receptor ST2 play an important role in mucosal barrier tissues, and seem to be crucial for Th2-cell mediated host defense. Galacto-oligosaccharides (GOS), used in infant formulas, exhibit gut and immune modulatory effects. To enhance our understanding of the immunomodulatory capacity of GOS, this study investigated the impact of dietary GOS intervention on IL-33 and ST2 expression related to intestinal barrier dysfunction and asthma.
  
  
  METHODS
  B6C3F1 and BALB/c mice were fed a control diet with or without 1% GOS. To simulate intestinal barrier dysfunction, B6C3F1 mice received a gavage with the mycotoxin deoxynivalenol (DON). To mimic asthma-like inflammatory airway responses, BALB/c mice were sensitized on day 0 and challenged on days 7-11 with house-dust mite (HDM) allergen. Samples from the intestines and lungs were collected for IL-33 and ST2 analysis by qRT-PCR, immunoblotting and immunohistochemistry.
  
  
  RESULTS
  Dietary GOS counteracted the DON-induced IL-33 mRNA expression and changed the IL-33 distribution pattern in the mouse small intestine. The IL-33 mRNA expression was positively correlated to the intestinal permeability. A strong positive correlation was also observed between IL-33 mRNA expression in the lung and the number of bronchoalveolar fluid cells. Reduced levels of IL-33 protein, altered IL-33 distribution and reduced ST2 mRNA expression were observed in the lungs of HDM-allergic mice after GOS intervention.
  
  
  CONCLUSIONS
  Dietary GOS mitigated IL-33 at the mucosal surfaces in a murine model for intestinal barrier dysfunction and HDM-induced asthma. This promising effect may open up new avenues to use GOS not only as a prebiotic in infant nutrition, but also as a functional ingredient that targets inflammatory processes and allergies associated with IL-33 expression.
authors: Division of Veterinary Pharmacy, Pharmacology and Toxicology, Utrecht University, Utrecht, The Netherlands.
authors: Kim A T
authors: KA
authors: Verheijden
authors: Peyman
authors: P
authors: Akbari
authors: Linette E M
authors: LE
authors: Willemsen
authors: Aletta D
authors: AD
authors: Kraneveld
authors: Gert
authors: G
authors: Folkerts
authors: Johan
authors: J
authors: Garssen
authors: Johanna
authors: J
authors: Fink-Gremmels
authors: Saskia
authors: S
authors: Braber
mesh_terms: D000067531:Alarmins; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004032:Diet; D005697:Galactosides / Q000008:administration & dosage / Q000276:immunology; D018928:Immunity, Mucosal; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33 / Q000235:genetics* / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009844:Oligosaccharides / Q000008:administration & dosage* / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014255:Trichothecenes / Q000633:toxicity
chemical_list: D000067531:Alarmins; D039741:Antigens, Dermatophagoides; D005697:Galactosides; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D007166:Immunosuppressive Agents; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D009844:Oligosaccharides; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D014255:Trichothecenes; C007262:deoxynivalenol