Low-molecular-weight components of placental extract inhibit degranulation by blocking Ca2+ influx in rat basophilic leukemia cells.

BACKGROUND: Placental extract (PE) is rich in peptides, amino acids, nucleic acids, vitamins, and minerals. Although PE is used for skin care and as a health food, it is also considered effective in the treatment of various diseases. Mast cells play an essential role in allergic diseases by secreting various inflammatory mediators, such as histamine, leukotrienes, and prostaglandins. PE has inhibitory effects on mast cell activation; however, the molecular mechanisms underlying these inhibitory effects remain unclear. The aim of this study was to investigate the mechanisms underlying the inhibitory effects of PE on mast cell activation. METHODS AND RESULTS: In this study, we used rat basophilic leukemia (RBL-2H3) cells as a mast cell model. We showed that short-term treatment with porcine PE (PPE) inhibited degranulation in a dose-dependent manner and demonstrated that this inhibitory effect was because of the blockade of extracellular Ca2⁺ influx rather than the inhibition of Ca2+ release from intracellular Ca2⁺ stores. In antigen-stimulated RBL-2H3 cells, PPE treatment did not affect the phosphorylation of Syk, an upstream signaling component, but inhibited the phosphorylation of ERK1/2, which modulates cytokine production. In addition, the molecular weights of the inhibitory components of PPE were found to be approximately 200-400 Da. CONCLUSIONS: Our results indicate that low-molecular-weight components of PPE inhibit mast cell degranulation by blocking Ca2+ influx. These findings are expected to contribute to the development of novel antiallergic drugs.