Involvement of the Antimicrobial Peptide Ll-37 in Human Atherosclerosis.
From: Cardiovascular Research Unit, Center for Molecular Medicine, Department of Medicine, CMM L8:03, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Arteriosclerosis, thrombosis, and vascular biology
- Publish Date: Jul 2006
- ISSN: 1524-4636
- Volume: 26
- Issue: 7
- Pages: 1551-7
- Medium: Internet
- Language: English
- Citation (JAMA): Edfeldt Kristina, Agerberth Birgitta, Rottenberg Martin E, et al. Involvement of the Antimicrobial Peptide Ll-37 in Human Atherosclerosis.. Arterioscler. Thromb. Vasc. Biol. Jul 2006;26:1551-7
Abstract
OBJECTIVE: Antimicrobial peptides are effector molecules of the innate immune system. To understand the function of vascular innate immunity in atherosclerosis, we investigated the role of LL-37, a cathelicidin antimicrobial peptide, in the disease process. METHODS AND RESULTS: Using real-time polymerase chain reaction, we found a 6-fold increase in human cationic antimicrobial protein 18/LL-37 transcript in human atherosclerotic lesions compared with normal arteries. Immunohistochemical analysis of atherosclerotic plaques showed that LL-37 was expressed mainly by macrophages and some endothelial cells. Western blot demonstrated existence of active LL-37 peptide and abundant proprotein in atheroma specimens. To understand the functional implication of LL-37 production in atherosclerosis, the transcription profile was assessed in endothelial cells treated with LL-37. Our data show that LL-37 induces expression of the adhesion molecule intercellular adhesion molecule-1 and the chemokine monocyte chemoattractant protein 1 in endothelial cells. Intriguingly, Chlamydia pneumoniae withstood the antimicrobial activity of LL-37 in vitro, although inflammatory response was induced on infection. CONCLUSIONS: LL-37 is produced in atherosclerotic lesions, where it may function as an immune modulator by activating adhesion molecule and chemokine expression, thus enhancing innate immunity in atherosclerosis.
Mesh Headings (Keywords): Antimicrobial Cationic Peptides, Atherosclerosis, Cells, Cultured, Chemokine CCL2, Chlamydophila Infections, Chlamydophila pneumoniae, Drug Resistance, Bacterial, Endothelial Cells, Humans, Immunity, Natural, Immunologic Factors, Inflammation, Intercellular Adhesion Molecule-1, Pneumonia, Bacterial, Protein Precursors, RNA, Messenger, Umbilical Veins
Check for Full Text / PubMed Unique Identifier (PMID): 16645154
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