RESUMEN
Some food-derived bioactive peptides exhibit prominent immunoregulatory activity. We previously demonstrated that the rice-derived PEP1 peptide, GIAASPFLQSAAFQLR, has strong immunological activity. However, the mechanism of this action is still unclear. In the present study, full-length transcripts of mouse dendritic cells (DC2.4) treated with PEP1 were sequenced using the PacBio sequencing platform, and the transcriptomes were compared via RNA sequencing (RNA-Seq). The characteristic markers of mature DCs, the cluster of differentiation CD86, and the major histocompatibility complex (MHC-II), were significantly upregulated after the PEP1 treatment. The molecular docking suggested that hydrogen bonding and electrostatic interactions played important roles in the binding between PEP1, MHC-II, and the T-cell receptor (TCR). In addition, the PEP1 peptide increased the release of anti-inflammatory factors (interleukin-4 and interleukin-10) and decreased the release of pro-inflammatory factors (interleukin-6 and tumor necrosis factor-α). Furthermore, the RNA-seq results showed the expression of genes involved in several signaling pathways, such as the NF-κB, MAPK, JAK-STAT, and TGF-ß pathways, were regulated by the PEP1 treatment, and the changes confirmed the immunomodulatory effect of PEP1 on DC2.4 cells. This findings revealed that the PEP1 peptide, derived from the byproduct of rice processing, is a potential natural immunoregulatory alternative for the treatment of inflammation.
Asunto(s)
Oryza , Animales , Ratones , Oryza/genética , Simulación del Acoplamiento Molecular , Péptidos/farmacología , Péptidos/metabolismo , Perfilación de la Expresión Génica , Células DendríticasRESUMEN
Inflammation is a contributing factor to the initiation and progression of many diseases, and some food-derived biofunctional peptides show high anti-inflammatory activity. In our previous study, we demonstrated that peptides derived from trypsin hydrolysis of rice protein show good immunological activity. In the present study, proteins of broken rice were extracted and identified by macroporous resin fractionation and liquid chromatography/tandem mass spectrometry (LC-MS/MS). Subsequently, a bioinformatics prediction and in silico simulation approach was used to screen for peptides showing anti-inflammatory activity, including inhibition of the production of nitric oxide and proinflammatory cytokines (interleukin-1ß, interleukin-6, and tumor necrosis factor-α) by lipopolysaccharide-stimulated RAW264.7 mice macrophages. Three peptides (DNIQGITKPAIR, IAFKTNPNSMVSHIAGK, and IGVAMDYSASSKR) that demonstrated the highest binding affinity were synthesized, and their in vitro anti-inflammatory activity was investigated. This is the first study that integrates LC-MS/MS identification and bioinformatics prediction for reporting the anti-inflammatory activity of anti-inflammatory peptides derived from broken rice protein. The study findings revealed that the peptides derived from the byproduct of rice milling could be potentially used as natural anti-inflammatory alternativities.