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1.
Allergol. immunopatol ; 40(1): 3-8, ene.-feb. 2012.
Article in English | IBECS | ID: ibc-96251

ABSTRACT

Background: The IL-15/NF-KappaB axis has an important role in coeliac disease (CD) and may represent a molecular target for immunomodulation. Ascorbate (vitamin C) is known to show inhibitory effects on NF-KappaB. Therefore, we studied if ascorbate supplementation to gliadin gliadin-stimulated biopsy culture could down-regulate the mucosal immune response to gliadin in CD. Methods: Duodenal biopsy explants from treated CD patients were gliadin challenged in vitro (100ìg/ml) with and without 20mM ascorbate. An extra tissue explant in basal culture was used as internal control. Secretion levels of nitrites (3h), and IFNGamma, TNFalpha, IFNalpha, IL-17, IL-13, and IL-6 (24h) were measured on the supernatants. IL-15 was assayed by western-blot on whole protein duodenal explants. Results: The addition of ascorbate to in vitro culture gliadin-challenged biopsies blocked the secretion of nitrites (p=0.013), IFNGamma (p=0.0207), TNFalpha (p=0.0099), IFNá (p=0.0375), and IL-6 (p=0.0036) compared to samples from non-ascorbate supplemented culture. Cytokine secretion was downregulated by ascorbate even to lower values than those observed in basal cultures (IFNGamma: p=0.0312; TNFalpha: p=0.0312; IFNá: p=0.0312; and IL-6: p=0.0078). Gliadin-challenge induced IL-15 production in biopsies from treated CD patients, while the addition of ascorbate to culture medium completely inhibited IL-15 production. Moreover, the inhibition of IL-15 by ascorbate took place even in the only treated CD-patient who had basal IL-15 production. Conclusions: Ascorbate decreases the mucosal inflammatory response to gluten in an intestinal biopsy culture model, so it might have a role in future supplementary therapy in CD(AU)


Subject(s)
Humans , Ascorbate Oxidase/pharmacokinetics , Immunity, Mucosal/physiology , Gliadin/pharmacokinetics , Celiac Disease/physiopathology , Inflammation/physiopathology , Interleukin-15/immunology , Ascorbic Acid/pharmacokinetics
2.
Allergol Immunopathol (Madr) ; 40(1): 3-8, 2012.
Article in English | MEDLINE | ID: mdl-21420224

ABSTRACT

BACKGROUND: The IL-15/NF-κB axis has an important role in coeliac disease (CD) and may represent a molecular target for immunomodulation. Ascorbate (vitamin C) is known to show inhibitory effects on NF-κB. Therefore, we studied if ascorbate supplementation to gliadin gliadin-stimulated biopsy culture could down-regulate the mucosal immune response to gliadin in CD. METHODS: Duodenal biopsy explants from treated CD patients were gliadin challenged in vitro (100 µg/ml) with and without 20mM ascorbate. An extra tissue explant in basal culture was used as internal control. Secretion levels of nitrites (3h), and IFNγ, TNFα, IFNα, IL-17, IL-13, and IL-6 (24h) were measured on the supernatants. IL-15 was assayed by western-blot on whole protein duodenal explants. RESULTS: The addition of ascorbate to in vitro culture gliadin-challenged biopsies blocked the secretion of nitrites (p=0.013), IFNγ (p=0.0207), TNFα (p=0.0099), IFNα (p=0.0375), and IL-6 (p=0.0036) compared to samples from non-ascorbate supplemented culture. Cytokine secretion was downregulated by ascorbate even to lower values than those observed in basal cultures (IFNγ: p=0.0312; TNFα: p=0.0312; IFNα: p=0.0312; and IL-6: p=0.0078). Gliadin-challenge induced IL-15 production in biopsies from treated CD patients, while the addition of ascorbate to culture medium completely inhibited IL-15 production. Moreover, the inhibition of IL-15 by ascorbate took place even in the only treated CD-patient who had basal IL-15 production. CONCLUSIONS: Ascorbate decreases the mucosal inflammatory response to gluten in an intestinal biopsy culture model, so it might have a role in future supplementary therapy in CD.


Subject(s)
Ascorbic Acid/pharmacology , Celiac Disease/drug therapy , Gliadin/immunology , Inflammation/prevention & control , Adult , Aged , Biopsy , Celiac Disease/immunology , Cytokines/biosynthesis , Female , Humans , Immunity, Mucosal/drug effects , Interleukin-15/antagonists & inhibitors , Interleukin-15/physiology , Male , Middle Aged
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