Collagen-Derived Dipeptides and Amino Acids Have Immunomodulatory Effects in M1-Differentiated RAW264.7 Cells and PBMC

Int J Mol Sci. 2023 Apr 8;24(8):6925. doi: 10.3390/ijms24086925.

Abstract

A number of food components, such as polyphenols and phytonutrients, have immunomodulatory effects. Collagen has various bioactivities, such as antioxidative effects, the promotion of wound healing, and relieving symptoms of bone/joint disease. Collagen is digested into dipeptides and amino acids in the gastrointestinal tract and subsequently absorbed. However, the difference in immunomodulatory effects between collagen-derived dipeptides and amino acids is unknown. To investigate such differences, we incubated M1 macrophages or peripheral blood mononuclear cells (PBMC) with collagen-derived dipeptides (hydroxyproline-glycine (Hyp-Gly) and proline-hydroxyproline (Pro-Hyp)) and amino acids (proline (Pro), hydroxyproline (Hyp), and glycine (Gly)). We first investigated the dose dependency of Hyp-Gly on cytokine secretion. Hyp-Gly modulates cytokine secretion from M1 macrophages at 100 µM, but not at 10 µM and 1 µM. We then compared immunomodulatory effects between dipeptides and mixtures of amino acids on M1 macrophages and PBMC. There was, however, no difference in cytokine secretion between dipeptides and their respective amino acids. We conclude that collagen-derived dipeptides and amino acids have immunomodulatory effects on M1-differentiated RAW264.7 cells and PBMC and that there is no difference in the immunomodulatory effects between dipeptides and amino acids.

Keywords: amino acids; collagen; cytokines; dipeptides; glycine; hydroxyproline; macrophages; proline.

MeSH terms

  • Amino Acids* / pharmacology
  • Collagen / metabolism
  • Cytokines
  • Dipeptides* / chemistry
  • Dipeptides* / pharmacology
  • Glycine
  • Hydroxyproline / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Proline / chemistry
  • Proline / pharmacology

Substances

  • Dipeptides
  • Hydroxyproline
  • Amino Acids
  • Collagen
  • Proline
  • Glycine
  • Cytokines