C. quinoa and S. hispanica L. Seeds Provide Immunonutritional Agonists to Selectively Polarize Macrophages.

Diet-related immunometabolic-based diseases are associated with chronic inflammation in metabolic tissues, and infiltrated macrophages have been suggested as mediators for tissue- damaging inflammation. Growing evidence implicates Chenopodium quinoa and Salvia hispanica L. as important contributors to immunonutritional health. However, the functional roles of the immunonutritional protease inhibitors (PPIs) found in these crops on the macrophages' metabolic and phenotypic adaptation remain to be elucidated. The salt soluble fraction of proteins was extracted and analyzed confirming the presence of 11S and 2S albumin. The <30 kDa fraction of the extract from both crops was subjected to simulated gastrointestinal digestion, where (RP-LC-MS/MS analyses) polypeptides from 2S-type of proteins were found, along with the 2S albumin (13 kDa) for S. hispanica in the bioaccessible fraction (BAF). Using human-like macrophage cells to deepen our understanding of the modulatory effects of this BAF, FACS analyses revealed their potential as TLR4 agonists, favoring increased phenotypic CD68/CD206 ratios. The results of mitochondrial stress tests showed that cells increased oxygen consumption rates and non-mitochondrial respiration, confirming negligible deleterious effects on mitochondrial function. At molecular-level, adaptation responses shed light on changes showing biological correlation with TLR4 signaling. The resulting immunometabolic effects triggered by PPIs can be a part of a tailored nutritional intervention strategy in immunometabolic-based diseases.

Gliadins induce TNFalpha production through cAMP-dependent protein kinase A activation in intestinal cells (Caco-2)

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Celiac disease is an autoimmune enteropathy caused by a permanent intolerance to gliadins. In this study the effects of two gliadin-derived peptides (PA2, PQPQLPYPQPQLP and PA9, QLQPFPQPQLPY) on TNFalpha production by intestinal epithelial cells (Caco-2) and whether these effects were related to protein kinase A (PKA) and/or -C (PKC) activities have been evaluated. Caco-2 cell cultures were challenged with several sets of gliadin peptides solutions (0.25 mg/mL), with/without different activators of PKA or PKC, bradykinin (Brdkn) and pyrrolidine dithiocarbamate (PDTC). The gliadin-derived peptides assayed represent the two major immunodominant epitopes of the peptide 33-mer of alpha-gliadin (56–88) (LQLQPFPQPQLPYPQPQLPYPQPQLPYPQPQPF). Both peptides induced the TNFalpha production triggering the inflammatory cell responses, the PA2 being more effective. The addition of the peptides in the presence of dibutyril cyclic AMP (cAMP), Brdkn or PDTC, inhibited the TNFalpha production. The PKC-activator phorbol 12-myristate 13-diacetate additionally increased the PA2- and PA9-induced TNFalpha production. These results link the gliadin-derived peptides induced TNFalpha production through cAMP-dependent PKA activation, where ion channels controlling calcium influx into cells could play a protective role, and requires NF-êB activation (AU)