Peptides Derived from Soybean β-Conglycinin Induce the Migration of Human Peripheral Polymorphonuclear Leukocytes

• Published in: Biological & pharmaceutical bulletin Vol. 46; no. 7; pp. 898 - 906
• Main Authors: Itagaki, Fumio, Kishimoto, Seishi, Watanabe, Machiko, Fujii, Norihiko, Yasuno, Nobuhiro, Nagashima, Kazuki, Oka, Saori, Yamashita, Atsushi
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.07.2023; Japan Science and Technology Agency
• Subjects: Calcium (intracellular); Calcium - metabolism; Cell differentiation; Cyclic AMP; Digestive enzymes; Elastase; Enzymes; formyl peptide receptor; Formyl peptides; Gene expression; Granulocytes; Humans; Leukocyte migration; Leukocytes; Leukocytes (polymorphonuclear); migration; Motility; Neutrophils - metabolism; Pancreatic elastase; peptide; Peptides; Peptides - pharmacology; Pertussis; Pertussis toxin; polymorphonuclear leukocyte; Promyeloid leukemia; real-time PCR; Retinoic acid; Soybean Proteins - metabolism; Soybean Proteins - pharmacology; soybean β-conglycinin; Soybeans; Trypsin; migration; formyl peptide receptor; peptide; soybean β-conglycinin; real-time PCR; polymorphonuclear leukocyte
• ISSN: 0918-6158; 1347-5215; 1347-5215
• DOI: 10.1248/bpb.b23-00010

Food-derived peptides have various biological activities. When food proteins are ingested orally, they are digested into peptides by endogenous digestive enzymes and absorbed by the immune cell-rich intestinal tract. However, little is known about the effects of food-derived peptides on the motility of human immune cells. In this study, we aimed to understand the effects of peptides derived from a soybean protein β-conglycinin on the motility of human peripheral polymorphonuclear leukocytes. We illustrated that MITL and MITLAIPVNKPGR, produced by digestion using in-vivo enzymes (trypsin and pancreatic elastase) of β-conglycinin, induces the migration of dibutyryl cAMP (Bt2 cAMP)-differentiated human promyelocytic leukemia 60 (HL-60) cells and human polymorphonuclear leukocytes in a dose- and time-dependent manner. This migration was more pronounced in Bt2 cAMP-differentiated HL-60 cells; mRNA expression of formyl peptide receptor (FPR) 1 increased significantly than in all-trans-retinoic acid (ATRA)-differentiated HL-60 cells. This migration was inhibited by tert-butoxycarbonyl (Boc)-MLP, an inhibitor of FPR, and by pretreatment with pertussis toxin (PTX). However, the effect was weak when treated with WRW4, a selective inhibitor of the FPR2. We then demonstrated that MITLAIPVNKPGR induced intracellular calcium responses in human polymorphonuclear leukocytes and Bt2 cAMP-HL60 cells. Furthermore, pre-treatment by fMLP desensitized the calcium response of MITLAIPVNKPGR in these cells. From the above, MITLAIPVNKPGR and MITL derived from soybean β-conglycinin induced polymorphonuclear leukocyte migration via the FPR1-dependent mechanism. We found chemotactic peptides to human polymorphonuclear leukocytes, which are the endogenous enzyme digests of soybean protein.