Involvement of the antimicrobial peptide LL-37 in human atherosclerosis.
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.


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.
Edfeldt
Kristina
K
Cardiovascular Research Unit, Center for Molecular Medicine, Department of Medicine, CMM L8:03, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Agerberth
Birgitta
B
Rottenberg
Martin E
ME
Gudmundsson
Gudmundur H
GH
Wang
Xiong-Biao
XB
Mandal
Kaushik
K
Xu
Qingbo
Q
Yan
Zhong-qun
ZQ
D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D050197:Atherosclerosis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D023521:Chlamydophila Infections / Q000097:blood; D016993:Chlamydophila pneumoniae / Q000502:physiology; D024881:Drug Resistance, Bacterial; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007155:Immunologic Factors / Q000378:metabolism*; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000097:blood; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D007155:Immunologic Factors; D011498:Protein Precursors; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D054804:Cathelicidins