Genomes and Genes
Gene Symbol: LL-37
Description: cathelicidin antimicrobial peptide
Alias: CAP-18, CAP18, CRAMP, FALL-39, FALL39, HSD26, LL37, cathelicidin antimicrobial peptide, 18 kDa cationic antimicrobial protein
- Kanda N, Ishikawa T, Kamata M, Tada Y, Watanabe S. Increased serum leucine, leucine-37 levels in psoriasis: positive and negative feedback loops of leucine, leucine-37 and pro- or anti-inflammatory cytokines. Hum Immunol. 2010;71:1161-71 pubmed publisher..In controls, negative feedback by LL-37 on TNF-α, IL-1β, IL-22, and IL-6 may exist. In both groups, negative feedback by LL-37 on IL-17 may exist. LL-37 may act as an effector and regulator. ..
- Xiao W, Hsu Y, Ishizaka A, Kirikae T, Moss R. Sputum cathelicidin, urokinase plasminogen activation system components, and cytokines discriminate cystic fibrosis, COPD, and asthma inflammation. Chest. 2005;128:2316-26 pubmed..IL)-8, IL-10, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, human cationic antimicrobial protein 18 (CAP18), urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor (PAI)-1 ..
- Coffelt S, Waterman R, Florez L, Honer zu Bentrup K, Zwezdaryk K, Tomchuck S, et al. Ovarian cancers overexpress the antimicrobial protein hCAP-18 and its derivative LL-37 increases ovarian cancer cell proliferation and invasion. Int J Cancer. 2008;122:1030-9 pubmed..These data provide further evidence of the existing relationship between pro-inflammatory molecules and ovarian cancer progression. ..
- Murakami M, Lopez Garcia B, Braff M, Dorschner R, Gallo R. Postsecretory processing generates multiple cathelicidins for enhanced topical antimicrobial defense. J Immunol. 2004;172:3070-7 pubmed..Thus, a single gene product encoding an important defense molecule alters structure and function in the topical environment to shift the balance of activity toward direct inhibition of microbial colonization. ..
- Liu P, Stenger S, Li H, Wenzel L, Tan B, Krutzik S, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311:1770-3 pubmed..These data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection. ..
- Stryjewski M, Hall R, Chu V, Kanafani Z, O Riordan W, Weinstock M, et al. Expression of antimicrobial peptides in the normal and involved skin of patients with infective cellulitis. J Infect Dis. 2007;196:1425-30 pubmed..These observations show, for the first time to our knowledge, that after infection the human body responds by increasing systemic innate immunity. ..
- Nell M, Tjabringa G, Vonk M, Hiemstra P, Grote J. Bacterial products increase expression of the human cathelicidin hCAP-18/LL-37 in cultured human sinus epithelial cells. FEMS Immunol Med Microbiol. 2004;42:225-31 pubmed..This suggests that bacterial products may stimulate innate immunity in the upper airways. ..
- Dorschner R, Lin K, Murakami M, Gallo R. Neonatal skin in mice and humans expresses increased levels of antimicrobial peptides: innate immunity during development of the adaptive response. Pediatr Res. 2003;53:566-72 pubmed..Quantitative real-time PCR showed mouse cathelicidin expression (CRAMP) is 10- to 100-fold greater in the perinatal period than adult...
- Gombart A, Bhan I, Borregaard N, Tamez H, Camargo C, Koeffler H, et al. Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis. Clin Infect Dis. 2009;48:418-24 pubmed publisher..2-11.2). In individuals initiating chronic hemodialysis, low baseline levels of hCAP18, a vitamin D-regulated antimicrobial protein, are independently associated with an increased risk of death attributable to infection. ..
- Hase K, Eckmann L, Leopard J, Varki N, Kagnoff M. Cell differentiation is a key determinant of cathelicidin LL-37/human cationic antimicrobial protein 18 expression by human colon epithelium. Infect Immun. 2002;70:953-63 pubmed
- Koczulla R, von Degenfeld G, Kupatt C, Krotz F, Zahler S, Gloe T, et al. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest. 2003;111:1665-72 pubmed..The human cathelicidin antimicrobial peptide LL-37/hCAP-18 is expressed in leukocytes and epithelial cells and secreted into wound and airway ..
- Elssner A, Duncan M, Gavrilin M, Wewers M. A novel P2X7 receptor activator, the human cathelicidin-derived peptide LL37, induces IL-1 beta processing and release. J Immunol. 2004;172:4987-94 pubmed..The human cathelicidin-derived peptide LL37 is a potent antimicrobial peptide produced predominantly by neutrophils and epithelial cells...
- Heilborn J, Nilsson M, Jimenez C, Sandstedt B, Borregaard N, Tham E, et al. Antimicrobial protein hCAP18/LL-37 is highly expressed in breast cancer and is a putative growth factor for epithelial cells. Int J Cancer. 2005;114:713-9 pubmed..These findings do not support the hypothesis that LL-37 has an antitumor effect, but rather suggest that hCAP18/LL-37 may promote tumor cell growth in breast cancer. ..
- Nagaoka I, Hirota S, Niyonsaba F, Hirata M, Adachi Y, Tamura H, et al. Cathelicidin family of antibacterial peptides CAP18 and CAP11 inhibit the expression of TNF-alpha by blocking the binding of LPS to CD14(+) cells. J Immunol. 2001;167:3329-38 pubmed..In this study we evaluated the LPS-neutralizing activities of cathelicidin peptides human CAP18 (cationic antibacterial proteins of 18 kDa) and guinea pig CAP11 using the CD14(+) murine macrophage cell line ..
- Malm J, Sørensen O, Persson T, Frohm Nilsson M, Johansson B, Bjartell A, et al. The human cationic antimicrobial protein (hCAP-18) is expressed in the epithelium of human epididymis, is present in seminal plasma at high concentrations, and is attached to spermatozoa. Infect Immun. 2000;68:4297-302 pubmed..Our results suggest a key role for hCAP-18 in the antibacterial integrity of the male reproductive system. The attachment of hCAP-18 to spermatozoa may implicate a role for hCAP-18 in conception. ..
- Ciornei C, Tapper H, Bjartell A, Sternby N, Bodelsson M. Human antimicrobial peptide LL-37 is present in atherosclerotic plaques and induces death of vascular smooth muscle cells: a laboratory study. BMC Cardiovasc Disord. 2006;6:49 pubmed..Immune cells can release antimicrobial peptides. One of these, human cathelicidin antimicrobial peptide hCAP-18, is cleaved by proteinase 3 generating a 4...
- Carretero M, Escamez M, Garcia M, Duarte B, Holguín A, Retamosa L, et al. In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37. J Invest Dermatol. 2008;128:223-36 pubmed..The protective and regenerative activities of LL-37 support its therapeutic potential to promote wound healing. ..
- Pistolic J, Cosseau C, Li Y, Yu J, Filewod N, Gellatly S, et al. Host defence peptide LL-37 induces IL-6 expression in human bronchial epithelial cells by activation of the NF-kappaB signaling pathway. J Innate Immun. 2009;1:254-67 pubmed publisher..Furthermore this host defence peptide augmented flagellin-mediated cytokine production, indicating that LL-37 likely modulates Toll-like receptor 5-mediated responses. ..
- Fukumoto K, Nagaoka I, Yamataka A, Kobayashi H, Yanai T, Kato Y, et al. Effect of antibacterial cathelicidin peptide CAP18/LL-37 on sepsis in neonatal rats. Pediatr Surg Int. 2005;21:20-4 pubmed..We conclude that LL-37 may prevent sepsis and be useful in lower doses for treating sepsis. However, LL-37 appears to have adverse effects when used at higher doses for treating sepsis. ..
- Cowland J, Johnsen A, Borregaard N. hCAP-18, a cathelin/pro-bactenecin-like protein of human neutrophil specific granules. FEBS Lett. 1995;368:173-6 pubmed..Thus, the 19 kDa protein is hCAP-18, stored as a 'pro-peptide' in specific granules. ..
- Yamasaki K, Schauber J, Coda A, Lin H, Dorschner R, Schechter N, et al. Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin. FASEB J. 2006;20:2068-80 pubmed..These observations demonstrate that the balance of proteolytic activity at an epithelial interface will control innate immune defense. ..
- Kai Larsen Y, Lüthje P, Chromek M, Peters V, Wang X, Holm A, et al. Uropathogenic Escherichia coli modulates immune responses and its curli fimbriae interact with the antimicrobial peptide LL-37. PLoS Pathog. 2010;6:e1001010 pubmed publisher..Taken together, our data demonstrate that biofilm components are involved in the pathogenesis of urinary tract infections by E. coli and can be a target of local immune defense mechanisms. ..
- Ganguly D, Chamilos G, Lande R, Gregorio J, Meller S, Facchinetti V, et al. Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med. 2009;206:1983-94 pubmed publisher..pDCs) sense self-DNA that is transported to endosomal TLR9 upon forming a complex with the antimicrobial peptide LL37. Whether LL37 also interacts with extracellular self-RNA and how this may contribute to DC activation in psoriasis ..
- Vandamme D, Landuyt B, Luyten W, Schoofs L. A comprehensive summary of LL-37, the factotum human cathelicidin peptide. Cell Immunol. 2012;280:22-35 pubmed publisher..Recent insights even indicate for a role of these peptides in cancer. This review provides a comprehensive summary of the most recent and relevant insights concerning the human cathelicidin LL-37. ..
- Tokumaru S, Sayama K, Shirakata Y, Komatsuzawa H, Ouhara K, Hanakawa Y, et al. Induction of keratinocyte migration via transactivation of the epidermal growth factor receptor by the antimicrobial peptide LL-37. J Immunol. 2005;175:4662-8 pubmed..The results of this study suggest that LL-37 closes skin wounds by the induction of keratinocyte migration. ..
- Kahlenberg J, Carmona Rivera C, Smith C, Kaplan M. Neutrophil extracellular trap-associated protein activation of the NLRP3 inflammasome is enhanced in lupus macrophages. J Immunol. 2013;190:1217-26 pubmed publisher..This leads to release of inflammatory cytokines that further stimulate NETosis, resulting in a feed-forward inflammatory loop that could potentially lead to disease flares and/or organ damage. ..
- Edström A, Malm J, Frohm B, Martellini J, Giwercman A, Morgelin M, et al. The major bactericidal activity of human seminal plasma is zinc-dependent and derived from fragmentation of the semenogelins. J Immunol. 2008;181:3413-21 pubmed..These data provide novel roles for the resolution of seminal clots and for the high zinc concentration in human seminal plasma. ..
- Kim S, Cha H, Kim D, Han G, Chung Y, Lee Y, et al. Antimicrobial peptide LL-37 is upregulated in chronic nasal inflammatory disease. Acta Otolaryngol. 2003;123:81-5 pubmed..IL-1beta and IL-8 transcripts exhibited a similar pattern to that of LL-37. We suggest that LL-37 is one of the antimicrobial peptides found in human nasal mucosa and that it participates in the innate immune system of the nasal mucosa. ..
- Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang Y, Homey B, et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature. 2007;449:564-9 pubmed..Here we identify the antimicrobial peptide LL37 (also known as CAMP) as the key factor that mediates pDC activation in psoriasis, a common autoimmune disease of ..
- Braff M, Hawkins M, Di Nardo A, Lopez Garcia B, Howell M, Wong C, et al. Structure-function relationships among human cathelicidin peptides: dissociation of antimicrobial properties from host immunostimulatory activities. J Immunol. 2005;174:4271-8 pubmed..Taken together, these observations suggest that proteolytic processing may alter the balance between cathelicidin antimicrobial and host immunostimulatory functions. ..
- Starner T, Agerberth B, Gudmundsson G, McCray P. Expression and activity of beta-defensins and LL-37 in the developing human lung. J Immunol. 2005;174:1608-15 pubmed..Lower levels of HBD-2 may be one factor contributing to the increased susceptibility of premature infants to pulmonary infections. ..
- Sørensen O, Gram L, Johnsen A, Andersson E, Bangsbøll S, Tjabringa G, et al. Processing of seminal plasma hCAP-18 to ALL-38 by gastricsin: a novel mechanism of generating antimicrobial peptides in vagina. J Biol Chem. 2003;278:28540-6 pubmed..This enzymatic activation of a proantimicrobial substance in seminal plasma following exposure to the vaginal milieu represents a novel mechanism to prevent infection following sexual intercourse. ..
- Heilborn J, Nilsson M, Kratz G, Weber G, Sørensen O, Borregaard N, et al. The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J Invest Dermatol. 2003;120:379-89 pubmed..Thus, we suggest that, in addition to being an anti-microbial peptide, LL-37 also plays a part in wound closure and that its reduction in chronic wounds impairs re-epithelialization and may contribute to their failure to heal. ..
- Sørensen O, Follin P, Johnsen A, Calafat J, Tjabringa G, Hiemstra P, et al. Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood. 2001;97:3951-9 pubmed..Blood. 2001;97:3951-3959) ..
- Filewod N, Pistolic J, Hancock R. Low concentrations of LL-37 alter IL-8 production by keratinocytes and bronchial epithelial cells in response to proinflammatory stimuli. FEMS Immunol Med Microbiol. 2009;56:233-40 pubmed publisher..These data indicate that low concentrations of LL-37 may alter epithelial responses to infecting microorganisms in vivo. ..
- Jeng L, Yamshchikov A, Judd S, Blumberg H, Martin G, Ziegler T, et al. Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. J Transl Med. 2009;7:28 pubmed publisher..Optimal vitamin D status may be important for innate immunity especially in the setting of sepsis. Further invention studies to examine this association are warranted. ..
- Zuyderduyn S, Ninaber D, Hiemstra P, Rabe K. The antimicrobial peptide LL-37 enhances IL-8 release by human airway smooth muscle cells. J Allergy Clin Immunol. 2006;117:1328-35 pubmed..LL-37 released by inflammatory cells may amplify inflammation through induction of IL-8 release by airway smooth muscle. ..
- Hertting O, Holm A, Lüthje P, Brauner H, Dyrdak R, Jonasson A, et al. Vitamin D induction of the human antimicrobial Peptide cathelicidin in the urinary bladder. PLoS ONE. 2010;5:e15580 pubmed publisher..In the light of the rapidly growing problem of resistance to common urinary tract antibiotics, we suggest that vitamin D may be a potential complement in the prevention of UTI. ..
- von Haussen J, Koczulla R, Shaykhiev R, Herr C, Pinkenburg O, Reimer D, et al. The host defence peptide LL-37/hCAP-18 is a growth factor for lung cancer cells. Lung Cancer. 2008;59:12-23 pubmed..The peptide activates tumour cells resulting in increased cell growth in vitro and in an animal model. The host defence peptide cathelicidin LL-37/hCAP-18 acts as growth factor for human lung cancer. ..
- Gudmundsson G, Agerberth B, Odeberg J, Bergman T, Olsson B, Salcedo R. The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes. Eur J Biochem. 1996;238:325-32 pubmed..A possible role for the cytokine interleukin-6 in the regulation of FALL 39 is discussed...
- Wantha S, Alard J, Megens R, van der Does A, Döring Y, Drechsler M, et al. Neutrophil-derived cathelicidin promotes adhesion of classical monocytes. Circ Res. 2013;112:792-801 pubmed publisher..Here, we show that neutrophil-derived cathelicidins (human: LL37, mouse: CRAMP) induce adhesion of classical monocytes but not of nonclassical monocytes in the mouse cremaster muscle and in in ..
- Bals R, Wang X, Zasloff M, Wilson J. The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. Proc Natl Acad Sci U S A. 1998;95:9541-6 pubmed..In summary, we show that LL-37/hCAP-18 is a peptide with broad antimicrobial activity that is secreted onto the airway surface from epithelial cells of the human lung. ..
- De Yang -, Chen Q, Schmidt A, Anderson G, Wang J, Wooters J, et al. LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med. 2000;192:1069-74 pubmed..Our results suggest that, in addition to its microbicidal activity, LL-37 may contribute to innate and adaptive immunity by recruiting neutrophils, monocytes, and T cells to sites of microbial invasion by interacting with FPRL1. ..
- Coffelt S, Marini F, Watson K, Zwezdaryk K, Dembinski J, LaMarca H, et al. The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells. Proc Natl Acad Sci U S A. 2009;106:3806-11 pubmed publisher..These data indicate that LL-37 facilitates ovarian tumor progression through recruitment of progenitor cell populations to serve as pro-angiogenic factor-expressing tumor stromal cells. ..
- Agerberth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L, et al. The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood. 2000;96:3086-93 pubmed
- Murakami M, Ohtake T, Dorschner R, Schittek B, Garbe C, Gallo R. Cathelicidin anti-microbial peptide expression in sweat, an innate defense system for the skin. J Invest Dermatol. 2002;119:1090-5 pubmed..Thus, sweat represents a unique mode of delivery for potent innate immune effector molecules in the absence of inflammation. ..
- Weber G, Chamorro C, Granath F, Liljegren A, Zreika S, Saidak Z, et al. Human antimicrobial protein hCAP18/LL-37 promotes a metastatic phenotype in breast cancer. Breast Cancer Res. 2009;11:R6 pubmed publisher..Our results provide evidence that hCAP18/LL-37 contributes to breast cancer metastasis. ..
- Bergman P, Johansson L, Asp V, Plant L, Gudmundsson G, Jonsson A, et al. Neisseria gonorrhoeae downregulates expression of the human antimicrobial peptide LL-37. Cell Microbiol. 2005;7:1009-17 pubmed..The results in this study suggest that pathogenic Neisseria may gain a survival advantage in the female genital tract by downregulating LL-37 expression...
- Nagaoka I, Tamura H, Hirata M. An antimicrobial cathelicidin peptide, human CAP18/LL-37, suppresses neutrophil apoptosis via the activation of formyl-peptide receptor-like 1 and P2X7. J Immunol. 2006;176:3044-52 pubmed..Suppression of neutrophil apoptosis results in the prolongation of their life span, and may be advantageous for host defense against bacterial invasion. ..
- Morizane S, Yamasaki K, Kabigting F, Gallo R. Kallikrein expression and cathelicidin processing are independently controlled in keratinocytes by calcium, vitamin D(3), and retinoic acid. J Invest Dermatol. 2010;130:1297-306 pubmed publisher..Thus, these variables may further control the functions of antimicrobial peptides in the skin. ..
- Agerberth B, Gunne H, Odeberg J, Kogner P, Boman H, Gudmundsson G. FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis. Proc Natl Acad Sci U S A. 1995;92:195-9 pubmed..RNA blot analyses disclosed that the gene for FALL-39 is expressed mainly in human bone marrow and testis. ..
- Yamasaki K, Di Nardo A, Bardan A, Murakami M, Ohtake T, Coda A, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med. 2007;13:975-80 pubmed