Gliadin and Collogen

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mle_ii
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Gliadin and Collogen

Post by mle_ii »

Cross linking to tissue transglutaminase and collagen favours gliadin toxicity in coeliac disease.
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum
BACKGROUND AND AIMS: Intestinal inflammation in coeliac disease is driven by the gluten fraction of wheat proteins. Deamidation or cross linking of gluten peptides by tissue transglutaminase (tTG), the coeliac disease autoantigen, creates potent T cell stimulatory peptides. Therefore, our aim was to identify the reaction patterns of gluten peptides, intestinal extracellular matrix proteins, and tTG. METHODS: tTG activity was analysed by incorporation of monodansyl cadaverine into gliadins. Fluorescence labelled tTG reactive short gliadin peptides were used to demonstrate their deamidation and explore their cross linking patterns with tTG itself or extracellular matrix proteins. Patient sera and controls were checked for autoantibodies to matrix proteins. RESULTS: Gliadins alpha1-alpha11, gamma1-gamma6, omega1-omega3, and omega5 were substrates for tTG. tTG catalysed the cross linking of gliadin peptides with interstitial collagen types I, III, and VI. Coeliac patients showed increased antibody titres against the collagens I, III, V, and VI. CONCLUSIONS: tTG formed high molecular weight complexes with all tested gliadins. As all tested gliadins were substrates for tTG, the tTG catalysed modifications were not restricted to single gliadin types and epitopes. Furthermore, haptenisation and long term immobilisation of gliadin peptides by tTG catalysed binding to abundant extracellular matrix proteins could be instrumental in the perpetuation of intestinal inflammation and some associated autoimmune diseases in coeliac disease.
Umm... not sure why I didn't put 1 and 1 together, but might this be part of the link between gluten and Collagenous colitis? Might serum anti-collagen antibodies be a potential test for CC?

Also take a look at this article:
Transglutaminase-independent binding of gliadin to intestinal
brush border membrane and GM1 ganglioside
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_DocSum
The part that you don't see without the full article is the following:
We evaluated the interaction of gliadin with intestinal
brush border membrane, which contains a high level of
GM1 ganglioside, by immunohistochemistry. Enzymatic
activity of transglutaminase was inhibited with EDTA to
eliminate TG2-mediated cross-linking of gliadin. This
caused the elimination of the strong binding of gliadin to
the lamina propria, but did not completely abolish its
binding to intestinal villi (Fig. 2). Gliadin proteins bound to
brush border epithelial cells in a pattern similar to the
interaction of cholera toxin, which specifically targets GM1
ganglioside.
So, I read here that tTG binds gliadin to the lamina propria, and even without tTG gliadin can also bind to intestinal villi. So in the first case you get anti-tissue transglutaminase, but in the second you would not. Might this explain why folks with gluten sensitivity and inflammation/damage don't produce anti-tTG.

Guess where in the intestine we can find a lot of these GM1 ganglioside components? In the ilium, as part of the M-Cells found in Peyers Patches. These M-Cells are the ones that sample the lumen for antigens. Might this be a cause for loss of tolerance or inflammation in general?

Mike
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