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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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