Proinflammatory responses driven by non-gluten factors are masked when they appear associated to gliadins

Cereal proteins are of clinical interest because of their cytotoxic and immunogenic features being associated to allergic processes and intestinal disorders. In addition to gliadins, there has been suggested an important role for non-gluten modulating factors (nGMF) on the onset of intestinal inflammatory processes. In this study, the amino acid sequences generated after a simulated human gastrointestinal (sGI) digestion of a commercial extract of gliadins (GEF) and the nGMF-enriched fraction (nGEF) obtained from them were characterized (nanoESI-qQTOF). These fractions were fed (20 days) to Wistar rats, sensitized with interferon (IFN)-γ (1000 IU/rat) and further treated with indomethacin (2 mg/kg). The production of inflammatory mediators (ELISAs) and the expression (rt-qPCR) of innate biomarkers was monitored in duodenal tissue sections. There were also evaluated changes in defined leukocyte (flow cytometry) populations quantified in peripheral blood samples. Expected nGMF components, CM3 and 0.19, as well as toxic gliadin-derived peptides were generated after sGI digestion. Rats fed with the nGEF showed higher concentrations of IFNγ, as well as expression levels of TLR-4 and the peroxisome proliferator activated receptor-α in duodenal samples than those animals fed with GEF. Rats fed with GEF showed higher expression levels of the endocannabinoid receptor-1 and an increased CD4(+)CD3(+)Foxp3(+) cell population. The data points out significant different cytotoxic and immunogenic potential of the nGEF when administered independently of the GEF to which are commonly associated. However, proinflammatory responses to nGMF are masked when present associated to gliadins.