A synthetic biotinylated peptide, BP21, inhibits the induction of mRNA expression of inflammatory substances by oxidized- and lyso-phosphatidylcholine.

Preclinical Research Oxidized low-density lipoprotein (ox-LDL) is implicated in many inflammatory diseases, e.g., type 2 diabetes, obesity, atherosclerosis, and metabolic syndrome. We previously reported that a synthetic biotinylated peptide, BP21, inhibits the bioactivity of ox-LDL via direct binding to ox-LDL. Here, we investigated the effect of BP21 on the mRNA expression of proinflammatory mediators induced by two major components of ox-LDL, oxidized- and lyso-phosphatidylcholine (ox-PC and LPC), in monocytes/macrophages (THP-1 cells) and adipocytes (3T3-L1 cells). In THP-1 cells, BP21 markedly reduced the mRNA expression of interleukin (IL)-6, adipocyte fatty acid-binding protein (aP2), tumor necrosis factor-α, and mitogen-activated protein kinase phosphatase-1, which are induced by one of the major bioactive components of ox-PC, 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC), and reduced the mRNA expression of IL-6, the ox-LDL-specific scavenger receptor CD36, and aP2 induced by LPC. In adipocytes, the mRNA expression of IL-1β as an adipokine and aP2 is highly induced by ox-PC and LPC, and BP21 markedly reduced the mRNA expression of IL-1β and aP2 induced by POVPC and LPC. Furthermore, BP21 specifically bound to LPC and POVPC in a dose-dependent manner. These results suggest that BP21 may be useful lead for the potential treatment and prevention of inflammatory diseases caused by ox-PC and LPC.