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A new study looks at innate immune response to gliadin. The innate immune
system responds to gliadin inducing zonulin release and increasing
intestinal permeability and may be a factor in the onset of celiac
disease, but I question if this leads "ultimately to the Ag-specific
adaptive immune response seen in patients with CD." This innate response
fails to explain why one identical twin may have celiac disease and not
the other. Both of the twins as well as people not even susceptable to
celiac disease would presumably have this same innate response to
gliadin. I once again urge celiac disease researchers to consider
a "gluten-internalizing" bacteria as being the necessary link to trigger
the onset of celiac disease. The presence or absence of such a bacteria
does indeed offer an explanation as to why one twin gets celiac disease
and not the other. Zonulin does not.
In the commercial supplement product, Glisodin, the properties of gliadin
have, in fact, already been used for the last few years to facilitate the
delivery of the antioxidant enzyme superoxide dismutase (SOD) protecting
it from digestive acids and getting it through the intestinal mucosa,
probably taking advantage of the zonulin effect. Aware of celiac
disease, the developer of Glisodin tried to use other peptides as a
carrier of SOD, but the only gliadin was effective. Unfortunately, this
denies celiacs the benefit of using Glisodin to treat oxidative stress.
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J Immunol. 2006 Feb 15;176(4):2512-21.
Gliadin Stimulation of Murine Macrophage Inflammatory Gene Expression and
Intestinal Permeability Are MyD88-Dependent: Role of the Innate Immune
Response in Celiac Disease.
Thomas KE, Sapone A, Fasano A, Vogel SN.
Department of Microbiology and Immunology.
Recent studies have demonstrated the importance of TLR signaling in
intestinal homeostasis. Celiac disease (CD) is an autoimmune enteropathy
triggered in susceptible individuals by the ingestion of gliadin-
containing grains. In this study, we sought to test the hypothesis that
gliadin initiates this response by stimulating the innate immune response
to increase intestinal permeability and by up-regulating macrophage
proinflammatory gene expression and cytokine production. To this end,
intestinal permeability and the release of zonulin (an endogenous mediator
of gut permeability) in vitro, as well as proinflammatory gene expression
and cytokine release by primary murine macrophage cultures, were measured.
Gliadin and its peptide derivatives, 33-mer and p31-43, were found to be
potent inducers of both a zonulin-dependent increase in intestinal
permeability and macrophage proinflammatory gene expression and cytokine
secretion. Gliadin-induced zonulin release, increased intestinal
permeability, and cytokine production were dependent on myeloid
differentiation factor 88 (MyD88), a key adapter molecule in the TLR/IL-1R
signaling pathways, but were neither TLR2- nor TLR4-dependent. Our data
support the following model for the innate immune response to gliadin in
the initiation of CD. Gliadin interaction with the intestinal epithelium
increases intestinal permeability through the MyD88-dependent release of
zonulin that, in turn, enables paracellular translocation of gliadin and
its subsequent interaction with macrophages within the intestinal
submucosa. There, the interaction of gliadin with macrophages elicits a
MyD88-dependent proinflammatory cytokine milieu that facilitates the
interaction of T cells with APCs, leading ultimately to the Ag-specific
adaptive immune response seen in patients with CD.
PMID: 16456012 [PubMed - in process]
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Phytother Res. 2004 Dec;18(12):957-62.
Supplementation with gliadin-combined plant superoxide dismutase extract
promotes antioxidant defences and protects against oxidative stress.
Vouldoukis I, Conti M, Krauss P, Kamate C, Blazquez S, Tefit M, Mazier D,
Calenda A, Dugas B.
ISOCELL Nutra SAS, 53 bd du General Martial Valin, 75015, Paris, France.
The potential benefits to health of antioxidant enzymes supplied either
through dietary intake or supplementation is still a matter of
controversy. The development of dietary delivery systems using wheat
gliadin biopolymers as a natural carrier represents a new alternative.
Combination of antioxidant enzymes with this natural carrier not only
delayed their degradation (i.e. the superoxide dismutase, SOD) during the
gastrointestinal digestive process, but also promoted, in vivo, the
cellular defences by strengthening the antioxidant status. The effects of
supplementation for 28 days with a standardized melon SOD extract either
combined (Glisodin) or not with gliadin, were evaluated on various
oxidative-stress biomarkers. As already described there was no change
either in superoxide dismutase, catalase or glutathione peroxidase
activities in blood circulation or in the liver following non-protected
SOD supplementation. However, animals supplemented with Glisodin showed a
significant elevation in circulated antioxidant enzymes activities,
correlated with an increased resistance of red blood cells to oxidative
stress-induced hemolysis. In the presence of Sin-1, a chemical donor of
peroxynitrites, mitochondria from hepatocytes regularly underwent membrane
depolarization as the primary biological event of the apoptosis cascade.
Hepatocytes isolated from animals supplemented with Glisodin presented a
delayed depolarization response and an enhanced resistance to oxidative
stress-induced apoptosis. It is concluded that supplementation with
gliadin-combined standardized melon SOD extract (Glisodin) promoted the
cellular antioxidant status and protected against oxidative stress-induced
cell death. 2004 John Wiley & Sons, Ltd.
PMID: 15742357 [PubMed - indexed for MEDLINE]
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