Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4
Yvonne Junker, Sebastian Zeissig, Seong-Jun Kim,Donatella Barisani, Herbert Wieser, Daniel A. Leffler, Victor Zevallos, Towia A. Libermann, Simon Dillon, Tobias L. Freitag, Ciaran P. Kelly, and Detlef Schuppan
J Exp Med. 2012 Dec 17; 209 (13): 2395–2408.
In this study, we show that members of the nongluten α-amylase/trypsin inhibitor (ATI) family contained in wheat and related cereals are strong inducers of innate immune responses in human and murine macrophages, monocytes, and DCs. ATI family members activate the TLR4–MD2–CD14 complex and elicit strong innate immune effects not only in vitro but also in vivo after oral or systemic challenge. Our findings have broad implications not only for celiac disease but also for other intestinal inflammatory disorders of the gastrointestinal tract.
Malav S. Trivedia, Jayni S. Shaha, Sara Al-Mughairya, Nathaniel W. Hodgsona, Benjamin Simmsa, Geert A. Trooskensb, Wim Van Criekingeb, Richard C. Detha, ,
Department of Pharmaceutical Sciences, Northeastern University, Boston, USA
Department of Mathematical Modelling, Statistics and Bioinformatics, Faculty of Bioscience Engineering, Ghent University, Belgium
The Journal of Nutritional Biochemistry
Volume 25, Issue 10, October 2014, Pages 1011–1018
Epigenetic programming, including CpG methylation and histone modifications, occurring during early postnatal development can influence the risk of disease in later life, and such programming may be modulated by nutritional factors such as milk and wheat, especially during the transition from a solely milk-based diet to one that includes other forms of nutrition.
The hydrolytic digestion of casein (a major milk protein) and gliadin (a wheat-derived protein) releases peptides with opioid activity, and in the present study, we demonstrate that these food-derived proline-rich opioid peptides modulate cysteine uptake in cultured human neuronal and gastrointestinal (GI) epithelial cells via activation of opioid receptors.
Restricted antioxidant capacity, caused by wheat- and milk-derived opioid peptides, may predispose susceptible individuals to inflammation and systemic oxidation, partly explaining the benefits of gluten-free or casein-free diets.
Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer.
Wheat amylase trypsin inhibitors as nutritional activators of innate immunity.
Food-derived opioid peptides inhibit cysteine uptake with redox and epigenetic consequences
Effect of Gliadin on Permeability of Intestinal Biopsy Explants from Celiac Disease Patients and Patients with Non-Celiac Gluten Sensitivity
Agrarian diet and diseases of affluence – Do evolutionary novel dietary lectins cause leptin resistance?
Insulin-Like Activity of Concanavalin A and Wheat Germ Agglutinin—Direct Interactions with Insulin Receptors
Effects of wheat germ agglutinin on insulin binding and insulin sensitivity of fat cells.
Interaction of Concanavalin A and Wheat Germ Agglutinin with the Insulin Receptor of Fat Cells and Liver
The Dietary Intake of Wheat and other Cereal Grains and Their Role in Inflammation
The effects of wheat germ agglutinin on the adipocyte insulin receptor.
Wheat-germ agglutinin mimics metabolic effects of insulin without increasing receptor autophosphorylation.
A peptide C-terminal to the second Zn finger of human vitamin D receptor is able to specify nuclear localization.
Antinutritive effects of wheat-germ agglutinin and other N-acetylglucosamine-specific lectins.
Effects of wheat germ agglutinin on human gastrointestinal epithelium: insights from an experimental model of immune/epithelial cell interaction.
Bound lectins that mimic insulin produce persistent insulin-like activities.
Immunocytology with Microwave-fixed Fibroblasts shows l tx,25-dihydroxyvitamin D3-dependent rapid and estrogen-dependent slow reorganization of Vitamin D receptors
Transcytotic pathway for blood-borne protein through the blood-brain barrier.
Wheat germ lectin induces G2/M arrest in mouse L929 fibroblasts.
Reduced plasma half-life of radio-labelled 25-hydroxyvitamin D3 in subjects receiving a high-fibre diet.
