The roles of cathelicidin LL-37 in immune defences and novel clinical applications

被引:252
作者
Nijnik, Anastasia [1 ]
Hancock, Robert E. W. [1 ]
机构
[1] Univ British Columbia, Dept Microbiol & Immunol, Ctr Microbial Dis & Immun Res, Lower Mall Res Stn 2259, Vancouver, BC V6T 1Z4, Canada
基金
美国国家卫生研究院; 加拿大健康研究院;
关键词
cathelicidin; host defence peptide; LL-37; ANTIMICROBIAL PEPTIDE LL-37; INVASIVE BACTERIAL-INFECTION; GROWTH-FACTOR RECEPTOR; HOST-DEFENSE; INNATE IMMUNITY; VITAMIN-D; CUTTING EDGE; ATOPIC-DERMATITIS; GENE-EXPRESSION; DENDRITIC CELLS;
D O I
10.1097/MOH.0b013e32831ac517
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Purpose of review LL-37 is the only member of the cathelicidin family of host defence peptides expressed LL in humans. It is primarily produced by phagocytic leucocytes and epithelial cells, and mediates a wide range of biological responses: direct killing of microorganisms, chemotaxis and chemokine induction, regulation of inflammatory responses, as well as adjuvant, angiogenic and wound healing effects. In this review we will cover the recent advances in the understanding of LL-37 biology: its activities, the mechanisms of its induction and roles in immune defence. Recent findings Recent studies advanced our understanding of the mechanisms controlling LL-37 expression, demonstrating the key involvement of the vitamin D-3 and the hypoxia response pathways, and the impacts of commensal and pathogenic microorganisms on its production. The synergistic and antagonistic interactions between LL-37 and other immune mediators have been further elucidated. Furthermore, studies in animal models and human patients further characterized the roles of cathelicidins in immunity, with roles in infectious and inflammatory conditions. The underlying properties of LL-37 have been exploited to create innate defence regulator peptides that represent a novel immunomodulatory approach to treating infections. Summary The understanding of the biological properties and functions of LL-37 and other host defence peptides advances our knowledge of innate immunity, the interactions of the host with pathogens and the microflora, as well as the pathology of infectious and inflammatory diseases, creating many strategies and opportunities for therapeutic intervention.
引用
收藏
页码:41 / 47
页数:7
相关论文
共 70 条
[31]   Cutting edge:: Vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin [J].
Liu, Philip T. ;
Stenger, Steffen ;
Tang, Dominic H. ;
Modlin, Robert L. .
JOURNAL OF IMMUNOLOGY, 2007, 179 (04) :2060-2063
[32]   Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response [J].
Liu, PT ;
Stenger, S ;
Li, HY ;
Wenzel, L ;
Tan, BH ;
Krutzik, SR ;
Ochoa, MT ;
Schauber, J ;
Wu, K ;
Meinken, C ;
Kamen, DL ;
Wagner, M ;
Bals, R ;
Steinmeyer, A ;
Zügel, U ;
Gallo, RL ;
Eisenberg, D ;
Hewison, M ;
Hollis, BW ;
Adams, JS ;
Bloom, BR ;
Modlin, RL .
SCIENCE, 2006, 311 (5768) :1770-1773
[33]   IFN-γ- and TNF-independent vitamin D-inducible human suppression of mycobacteria:: The role of cathelicidin LL-37 [J].
Martineau, Adrian R. ;
Wilkinson, Katalin A. ;
Newton, Sandra M. ;
Floto, R. Andres ;
Norman, Anthony W. ;
Skolimowska, Keira ;
Davidson, Robert N. ;
Sorensen, Ole E. ;
Kampmann, Beate ;
Griffiths, Christopher J. ;
Wilkinson, Robert J. .
JOURNAL OF IMMUNOLOGY, 2007, 178 (11) :7190-7198
[34]   Developmental switch of intestinal antimicrobial peptide expression [J].
Menard, Sandrine ;
Foerster, Valentina ;
Lotz, Michael ;
Guetle, Dominique ;
Duerr, Claudia U. ;
Gallo, Richard L. ;
Henriques-Normark, Birgitta ;
Puetsep, Katrin ;
Andersson, Mats ;
Glocker, Erik O. ;
Hornef, Mathias W. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2008, 205 (01) :183-193
[35]   Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37 [J].
Mookherjee, N ;
Brown, KL ;
Bowdish, DME ;
Doria, S ;
Falsafi, R ;
Hokamp, K ;
Roche, FM ;
Mu, RX ;
Doho, GH ;
Pistolic, J ;
Powers, JP ;
Bryan, J ;
Brinkman, FSL ;
Hancock, REW .
JOURNAL OF IMMUNOLOGY, 2006, 176 (04) :2455-2464
[36]   Cathelicidins and functional analogues as antisepsis molecules [J].
Mookherjee, Neeloffer ;
Rehaume, Linda M. ;
Hancock, Robert E. W. .
EXPERT OPINION ON THERAPEUTIC TARGETS, 2007, 11 (08) :993-1004
[37]   An antimicrobial cathelicidin peptide, human CAP18/LL-37, suppresses neutrophil apoptosis via the activation of formyl-peptide receptor-like 1 and P2X7 [J].
Nagaoka, Isao ;
Tamura, Hiroshi ;
Hirata, Michimasa .
JOURNAL OF IMMUNOLOGY, 2006, 176 (05) :3044-3052
[38]  
Niyonsaba F, 2001, EUR J IMMUNOL, V31, P1066, DOI 10.1002/1521-4141(200104)31:4<1066::AID-IMMU1066>3.0.CO
[39]  
2-#
[40]  
Niyonsaba F, 2002, IMMUNOLOGY, V106, P20, DOI 10.1046/j.1365-2567.2002.01398.x