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    Roy Jamron
    Roy Jamron

    Role of the Innate Immune Response in Celiac Disease with Comments by Roy Jamron

    Reviewed and edited by a celiac disease expert.

    Celiac.com 04/10/2006 - This 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 celiac disease. 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 susceptible to celiac disease would presumably have this same innate response to gliadin. I again urge celiac disease researchers to consider Open Original Shared Link as the necessary trigger for the onset of celiac disease. The presence or absence of such bacteria does indeed offer an explanation as to why one twin gets celiac disease and not the other. Open Original Shared Link 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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    Abstract of Study:

    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 (celiac disease) 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 celiac disease. 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 celiac disease.



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    Guest Kodi

    Great article! I wonder if any celiac patient could have an adverse reaction to GliSODin, or if it is even a theoretical possibility.

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    Guest Gene Tinsley

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    what a great site and informative posts, I will add a backlink and bookmark your site. Keep up the good work!

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  • About Me

    Roy Jamron

    Roy S. Jamron holds a B.S. in Physics from the University of Michigan and an M.S. in Engineering Applied Science from the University of California at Davis, and independently investigates the latest research on celiac disease and related disorders.


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