ИСТИНА

Gluten is the name of a family of storage proteins from cereals, which play a crucial role in celiac disease pathogenesis due to their immunogenic regions resistance to gastro-intestinal proteases. In the present work, gluten proteins from wheat, rye, barley and oat were digested by wheat-derived papain-like cysteine protease triticain-a. MALDI-TOF spectrometry revealed triticain-a cleavage sites presented within immunogenic regions of gluten-related proteins of wheat, rye, barley and oat. Toxicity of gluten-derived products were analyzed on CaCo-2 cells monolayer treated with peptides obtained by pepsin-trypsin and triticain-a-pepsin-trypsin gluten digestion (PT- and TrcPT-). Measurements of transepithelial electrical resistance (TEER) of CaCo-2 cells monolayer treated with TrcPT-peptides showed that this treatment causes less damage then the treatm ent of the monolayer with PT-peptides revealing protective eff ect of additional triticain-a digestion. Il-1b and TNF-a are known as infl ammatory mediators of, in particular, intestinal infl ammation and, therefore, were further used to evaluate infl ammatory responses in monolayer treated with PT- and TrcPTgluten peptides. To sum up, cleavage sites of triticain-a-mediated digestion of gluten proteins sourced from diff erent origins were determined. Moreover, the decreased toxicity of triticain-a-digested gluten-derived peptides on CaCo-2 cells monolayer at conditions mimicking gastro-intestinal tract was demonstrated. Together these data suggest triticain-a as a promising agent for celiac disease treatment. Th is work was funded by the Russian Science Foundation (grant #16-15-10410).