Regulation of the Proinflammatory Activity of the RBL-2H3 Cells by Activated Protein C and Peptide-Agonist of Protease-Activated Receptor 1 (PAR1)

The present study is focused on the problem of regulation of the proinflammatory activity of mast cells through a specific class of protease-activated receptors, PAR1. Here we show for the first time that a new peptide-agonist of PAR1 regulates the activity of the mast cells analog, cell line RBL-2H3. The peptide-agonist of PAR1, like activated protein C (APC), exerts anti-inflammatory and cytoprotective effects on RBL-2H3 cells, when they are activated by proinflammatory factors. Incubation of mast cells with lipopolysaccharide (LPS) induces a transient increase in the intracellular concentration of free calcium ions, enhances the histamine secretion, and suppresses cell proliferation. Pretreatment of the cells with the peptide or APC prevents the effect of endotoxin. Activation of the RBL-2H3 cells by thrombin and calcium ionophore leads to actin reorganization, which may indicate cell activation and secretion onset. Application of the peptide or APC in the presence of activators leads to the actin ordering in the cell submembrane region, which is typical for the control group. Thus, the newly discovered anti-inflammatory and protective properties of the peptide-agonist of PART (NPNDKYEPF-amide) open up the possibility of finding new approaches to the therapy of inflammatory processes on the basis of peptide drugs through the modulation of the PAR activity.