title: Involvement of the antimicrobial peptide LL-37 in human atherosclerosis.
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.
  
  
  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.
authors.affiliation: Cardiovascular Research Unit, Center for Molecular Medicine, Department of Medicine, CMM L8:03, Karolinska University Hospital, 171 76 Stockholm, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Edfeldt
authors.forename: Birgitta
authors.initials: B
authors.lastname: Agerberth
authors.forename: Martin E
authors.initials: ME
authors.lastname: Rottenberg
authors.forename: Gudmundur H
authors.initials: GH
authors.lastname: Gudmundsson
authors.forename: Xiong-Biao
authors.initials: XB
authors.lastname: Wang
authors.forename: Kaushik
authors.initials: K
authors.lastname: Mandal
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Xu
authors.forename: Zhong-qun
authors.initials: ZQ
authors.lastname: Yan
mesh_terms: 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
chemical_list: 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