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

被引：48

作者：

Hecht, Iris ^{[1
]}

Rong, Jiang ^{[2
,3
]}

Sampaio, Andre L. F. ^{[4
]}

Hermesh, Chen ^{[1
]}

Rutledge, Caleb ^{[2
,3
]}

Shemesh, Ronen ^{[1
]}

Toporik, Amir ^{[1
]}

Beiman, Merav ^{[1
]}

Dassa, Liat ^{[1
]}

Niv, Hagit ^{[1
]}

Cojocaru, Gady ^{[1
]}

Zauberman, Arie ^{[1
]}

Rotman, Galit ^{[1
]}

Perretti, Mauro ^{[4
]}

Vinten-Johansen, Jakob ^{[2
,3
]}

Cohen, Yossi ^{[1
]}

机构：

[1] Compugen Ltd, IL-69512 Tel Aviv, Israel

[2] Emory Univ, Carlyle Fraser Heart Ctr, Atlanta, GA 30322 USA

[3] Emory Crawford Long Hosp, Atlanta, GA USA

[4] Barts & London Med Sch, William Harvey Res Inst, London, England

来源：

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS | 2009年 / 328卷 / 02期

关键词：

ISCHEMIA-REPERFUSION INJURY; INTERCELLULAR-ADHESION MOLECULE-1; REDUCES INFARCT SIZE; MYOCARDIAL-ISCHEMIA; MONOCLONAL-ANTIBODY; NEUTROPHIL ACCUMULATION; INDUCED COLITIS; A(4); INFLAMMATION; ANALOG;

D O I：

10.1124/jpet.108.145821

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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

引用

页码：426 / 434

页数：9

共 40 条

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