Gliadin p31-43, an undigested peptide derived from gliadin, prompts an innate immune response in the intestine and disrupts endocytic trafficking. Moreover, its utilization in celiac disease research has proven beneficial.

Treatment with gliadin p31-43 (100μg/mL; 30 minutes-6 hours) stimulates the formation of MyD88/TLR7 complexes and activates downstream signaling pathways by enhancing MAPKs, ERK, JNK, and p38 activation in CaCo-2 cells. This results in increased levels of phosphorylated pY-ERK, JNK (pY-JNK), and p38 (pY-p38). Additionally, gliadin p31-43 treatment elevates NF-κB phosphorylation from 0.45 in control cells to 0.86 and significantly boosts MxA protein levels. It also affects the levels of IFN-α 7 and 17 mRNAs. Further, gliadin p31-43 localizes to early endosomes, interfering with the proper positioning of the HRS to early endosomes and delaying endocytic vesicle maturation. Western Blot Analysis confirms these findings, showing an increase in MyD88/TLR7 complex formation and elevated TLR7 levels following gliadin p31-43 exposure.

Gliadin p31-43, administered intraluminally at a dose of 10 μg, naturally forms structured oligomers and aggregates in vitro, triggering the apoptosis-associated speck-like (ASC) complex[2]. Additionally, oral administration of 20 μg of Gliadin p31-43 in wild type C57Bl/6 mice elevates IL-1β levels, indicating the activation of the inflammasome caspase-1 pathway in the small intestine mucosa. This demonstrates Gliadin p31-43's inherent ability to initiate the NLRP3 inflammasome[2], showcasing its sequence-specific spontaneous action.