Wheat Amylase Trypsin Inhibitors Aggravate Intestinal Inflammation Associated with Celiac Disease Mediated by Gliadin in BALB/c Mice

Abstract

Celiac disease (CD) is an autoimmune intestinal disorder caused by the ingestion of gluten in people who carry the susceptible gene. In current celiac disease research, wheat gluten is often the main target of attention, neglecting the role played by non-gluten proteins. This study aimed to describe the effects of wheat amylase trypsin inhibitors (ATI, non-gluten proteins) and gliadin in BALB/c mice while exploring the further role of relevant adjuvants (cholera toxin, polyinosinic: polycytidylic acid and dextran sulfate sodium) intervention. An ex vivo splenocyte and intestinal tissue were collected for analysis of the inflammatory profile. The consumption of gliadin and ATI caused intestinal inflammation in mice. Moreover, the histopathology staining of four intestinal sections (duodenum, jejunum, terminal ileum, and middle colon) indicated that adjuvants, especially polyinosinic: polycytidylic acid, enhanced the villi damage and crypt hyperplasia in co-stimulation with ATI and gliadin murine model. Immunohistochemical results showed that tissue transglutaminase and IL-15 expression were significantly increased in the jejunal tissue of mice treated with ATI and gliadin. Similarly, the expression of inflammatory factors (TNF-α, IL-1β, IL-4, IL-13) and Th1/Th2 balance also showed that the inflammation response was significantly increased after co-stimulation with ATI and gliadin. This study provided new evidence for the role of wheat amylase trypsin inhibitors in the pathogenesis of celiac disease.

Does sourdough bread provide clinically relevant health benefits?

“…Similar to prolamins, the clinical relevance of ATIs and nsLTPs is attributed to their resistance to proteolysis and acid or heat exposure. In vitro studies revealed that, in addition to the well-recognized immune reaction to prolamins, CD is also associated with a humoral immune response directed against serpins (serine protease inhibitors), purinins, ATIs, globulins, farinins and lectins, also known as wheat germ agglutinin ( 40 , 43 , 44 , 140 ). However, lectins are not heat stable and lose their adverse biological effects as a result of heat exposure, such as cooking or baking ( 140 ).…”

Beta1-adrenergic receptor autoantibodies contributes to atrial remodeling by PTEN-mediated repression ofcardiomyocyte autophagy and aggravation of cardiomyocyte apoptosis

“…Each eld of view was magni ed 20 times, and the images were quanti ed using ImageJ software (version 1.8.0). The average optical density (AOD) was used to calculate the areas of immunohistochemically positive cells [19].…”

Absolute and relative quantitation of amylase/trypsin-inhibitors by LC-MS/MS from wheat lines obtained by CRISPR-Cas9 and RNAi

“…Furthermore, ATIs are the triggers of Bakers’ asthma, a wheat allergy, which affects up to 10% of flour workers ( Salcedo et al, 2011 ; Huebener et al, 2015 ). Recent, studies indicated that ATIs might even have the potential to cause celiac disease ( Huebener et al, 2015 ; Yu et al, 2022 ) or are recognized by gluten-detecting enzyme-linked immunosorbent assays ( Fraberger et al, 2020 ). Nevertheless, the role of ATIs in celiac disease is scarcely investigated so far and occurrence of them in gluten (isolates) ( Wieser and Scherf, 2018 ; Lexhaller et al, 2019 ) even increases the complexity of this question.…”