2017
DOI: 10.1038/s41598-017-13709-1
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Interfering with the high-affinity interaction between wheat amylase trypsin inhibitor CM3 and toll-like receptor 4: in silico and biosensor-based studies

Abstract: Wheat amylase/trypsin bi-functional inhibitors (ATIs) are protein stimulators of innate immune response, with a recently established role in promoting both gastrointestinal and extra-gastrointestinal inflammatory syndromes. These proteins have been reported to trigger downstream intestinal inflammation upon activation of TLR4, a member of the Toll-like family of proteins that activates signalling pathways and induces the expression of immune and pro-inflammatory genes. In this study, we demonstrated the abilit… Show more

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Cited by 35 publications
(40 citation statements)
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“…ATIs represent 2%-4% of total wheat protein and are believed to induce an innate immune response via activation of the Toll-like receptor 4 (TLR4) on immune cells within the intestine. They have also been shown to be involved in an adaptive immune response, have been implicated in coeliac disease, and may also contribute to inflammation in other disorders [48][49][50][51]. Additionally, legumes, which have a higher protein content than cereals, contain significant levels of anti-nutritional factors such as lectins and trypsin inhibitors, and two major storage proteins, vicilins and legumins, which are all resistant to proteolysis in the small intestine [46,52,53].…”
Section: Resistant Proteins-beyond Glutenmentioning
confidence: 99%
“…ATIs represent 2%-4% of total wheat protein and are believed to induce an innate immune response via activation of the Toll-like receptor 4 (TLR4) on immune cells within the intestine. They have also been shown to be involved in an adaptive immune response, have been implicated in coeliac disease, and may also contribute to inflammation in other disorders [48][49][50][51]. Additionally, legumes, which have a higher protein content than cereals, contain significant levels of anti-nutritional factors such as lectins and trypsin inhibitors, and two major storage proteins, vicilins and legumins, which are all resistant to proteolysis in the small intestine [46,52,53].…”
Section: Resistant Proteins-beyond Glutenmentioning
confidence: 99%
“…58 Os efeitos citotóxicos poderiam ser explicados pelos inibidores da alfa-amilase/tripsina do trigo, os quais poderiam ser o gatilho para a resposta imune inata, promovendo a liberação de citocinas por monócitos, macrófagos e células dendríticas. 25,59,[66][67][68][69] Segundo Volta et al, possíveis mecanismos fisiopatológicos da SNCG/T incluem ativação imune inata e adaptativa, barreira epitelial intestinal prejudicada e alterações no microbioma intestinal. Estes fatores interligados podem ser explorados por sua relevância clínica como possíveis biomarcadores.…”
Section: O Glútenunclassified
“…Although all the three proteins induced degranulation, the most effective one was CM3, accounting for the important role played by this protein in triggering allergic reactions. Moreover, CM3 has an important role in innate immune response, at least in monocytes, macrophages, and dendritic cells [12,13].…”
Section: Introductionmentioning
confidence: 99%