The Amelioration of Methionine Restriction on the Celiac Toxic Effects of p31–43 Gliadin Peptide Is Disrupted by S-Adenosyl-Methionine

ABSTRACT

Methionine restriction (MR) has been found to alleviate the progression of diseases such as cognitive disorders and cancer, but it is not clear whether regulating methionine availability can have a beneficial effect on wheat gluten-induced celiac disease. We aimed to excavate the effects of MR on the celiac toxic effects of p31–43 gliadin peptide. In this study, we systematically investigated the effects of MR on p31–43 gliadin peptide-induced oxidative damage, the elevation of tissue transglutaminase enzyme activity, the overexpression of inflammatory factors, the increase of permeability, and T-lymphocyte dysfunction by utilizing Caco-2 epithelial cells and lymphocytes derived from mouse mesenteric lymph nodes to elucidate the effectiveness of MR. Moreover, the potential mechanism of MR on innate and adaptive immune regulation was explored with the help of S-adenosyl-methionine (SAM), a critical metabolic intermediate in methionine cycle. We discovered that MR effectively suppressed the celiac toxic effects of p31–43 gliadin peptide. Furthermore, we illustrated the controlling role of SAM in MR to regulate the toxic effects of gliadin in terms of both gliadin-induced innate and adaptive immune responses and found that SAM could directly affect the effectiveness of MR. This study might offer novel insights for the utilization of MR in celiac disease (such as MR interventions or gluten-free diets with specific methionine content) as well as the roles of SAM in MR.