A Novel Peptide Agonist of Formyl-Peptide Receptor-Like 1 (ALX) Displays Anti-Inflammatory and Cardioprotective Effects

• DOI: 10.1124/jpet.108.145821
• Publication Date: 2008-11-21T02:26:01Z
• Authors: Iris Hecht; Jiang Rong; André L.F. Sampaio; Chen Hermesh; Caleb Rutledge; Ronen Shemesh; Amir Toporik; Merav Beiman; Liat Dassa; Hagit Niv; Gady Cojocaru; Arie Zauberman; Galit Rotman; Mauro Perretti; Jakob Vinten-Joha...; Yossi Cohen
• Keywords: Proinflammatory cytokine; Formyl peptide receptor; Proteolysis

Activation of the formyl-peptide receptor-like (FPRL) 1 pathway has recently gained high recognition for its significance in therapy inflammatory diseases. Agonism at FPRL1 affords a beneficial effect animal models acute conditions, as well chronic TIPMFVPESTSKLQKFTSWFM-amide (CGEN-855A) is novel 21-amino acid peptide agonist and also activates FPRL2. CGEN-855A was discovered using computational platform designed to predict G protein-coupled receptor agonists cleaved from secreted proteins by convertase proteolysis. In vivo, displays anti-inflammatory activity manifested 50% inhibition polymorphonuclear neutrophil (PMN) recruitment inflamed air pouch provides protection against ischemia-reperfusion-mediated injury myocardium both murine rat (36 25% reduction infarct size, respectively). Both these activities are accompanied PMN injured organ. The secretion cytokines, including interleukin (IL)-6, IL-1beta, tumor necrosis factor-alpha, not affected upon incubation human peripheral blood mononuclear cells with CGEN-855A, whereas IL-8 elevated up 2-fold treatment highest dose only. Collectively, new data support potential role reperfusion-mediated other conditions.