The effects of diketopiperazines from Callyspongia sp. on release of cytokines and chemokines in cultured J774A.1 macrophages.

Diketopiperazines (DKPs) are a class of secondary metabolites that result from peptide bonds between two amino acids to form a lactam. Due to their rigid structure, chiral nature, and varied side chains, DKPs have been of research interest for their diverse bioactivities. However, little is known about whether DPKs stimulate the release of cytokine and chemokines in macrophage cells. The present aim was to study the effect of DKPs firstly isolated from sponge Callyspongia sp. on the release of several cytokines in murine macrophage-like cell line J774A.1 after stimulation in vitro, and their potential structure-activity relationship of five natural DKPs on four representative cytokines, interferon-γ (IFN-γ), pro-inflammatory (tumor necrosis factor, TNF-α), anti-inflammatory cytokine (interleukin-10, IL-10), and chemokine (monocyte chemoattractant protein-1, MCP-1). Results suggested that these five DKPs, especially DKP 1 bearing 3-hydroxyl-l-proline (l-Hyp), might be useful as a promising macrophage cytokines stimulator.