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
[1]   Transfer of a cathelicidin peptide antibiotic gene restores bacterial killing in a cystic fibrosis xenograft model [J].
Bals, R ;
Weiner, DJ ;
Meegalla, RL ;
Wilson, JM .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (08) :1113-1117
[2]   The human cationic host defense peptide LL-37 mediates contrasting effects on apoptotic pathways in different primary cells of the innate immune system [J].
Barlow, Peter G. ;
Li, Yuexin ;
Wilkinson, Thomas S. ;
Bowdish, Dawn M. E. ;
Lau, Y. Elaine ;
Cosseau, Celine ;
Haslett, Christopher ;
Simpson, A. John ;
Hancock, Robert E. W. ;
Davidson, Donald J. .
JOURNAL OF LEUKOCYTE BIOLOGY, 2006, 80 (03) :509-520
[3]   The human cationic peptide LL-37 induces activation of the extracellular signal-regulated kinase and p38 kinase pathways in primary human monocytes [J].
Bowdish, DME ;
Davidson, DJ ;
Speert, DP ;
Hancock, REW .
JOURNAL OF IMMUNOLOGY, 2004, 172 (06) :3758-3765
[4]   Impact of LL-37 on anti-infective immunity [J].
Bowdish, DME ;
Davidson, DJ ;
Lau, YE ;
Lee, K ;
Scott, MG ;
Hancock, REW .
JOURNAL OF LEUKOCYTE BIOLOGY, 2005, 77 (04) :451-459
[5]   Complexities of targeting innate immunity to treat infection [J].
Brown, Kelly L. ;
Cosseau, Celine ;
Gardy, Jennifer L. ;
Hancock, Robert E. W. .
TRENDS IN IMMUNOLOGY, 2007, 28 (06) :260-266
[6]   Lysozyme-modified probiotic components protect rats against polymicrobial sepsis: Role of macrophages and cathelicidin-related innate immunity [J].
Bu, Heng-Fu ;
Wang, Xiao ;
Zhu, Ya-Qin ;
Williams, Roxanne Y. ;
Hsueh, Wei ;
Zheng, Xiaotian ;
Rozenfeld, Ranna A. ;
Zuo, Xiu-Li ;
Tan, Xiao-Di .
JOURNAL OF IMMUNOLOGY, 2006, 177 (12) :8767-8776
[7]   In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37 [J].
Carretero, Marta ;
Escamez, Maria J. ;
Garcia, Marta ;
Duarte, Blanca ;
Holguin, Almudena ;
Retamosa, Luisa ;
Jorcano, Jose L. ;
del Rio, Marcela ;
Larcher, Fernando .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2008, 128 (01) :223-236
[8]   The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection [J].
Chromek, Milan ;
Slamova, Zuzana ;
Bergman, Peter ;
Kovacs, Laszlo ;
Podracka, L'udmila ;
Ehren, Ingrid ;
Hokfelt, Tomas ;
Gudmundsson, Gudmundur H. ;
Gallo, Richard L. ;
Agerberth, Birgitta ;
Brauner, Annelie .
NATURE MEDICINE, 2006, 12 (06) :636-641
[9]  
Cole AM, 2006, CURR TOP MICROBIOL, V306, P199
[10]   The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization [J].
Davidson, DJ ;
Currie, AJ ;
Reid, GSD ;
Bowdish, DME ;
MacDonald, KL ;
Ma, RC ;
Hancock, REW ;
Speert, DP .
JOURNAL OF IMMUNOLOGY, 2004, 172 (02) :1146-1156