A comprehensive summary of LL-37, the factotum human cathelicidin peptide

Vandamme, Dieter; Landuyt, Bart; Luyten, Walter; Schoofs, Liliane

doi:10.1016/j.cellimm.2012.11.009

Cited by 479 publications

(484 citation statements)

References 183 publications

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“…This was first shown in tuberculosis, where the traditional treatments with sunlight and cod liver oil, rich in vitamin D, are viewed in a new light after the discovery of antimicrobial peptides induced by vitamin D. The two antimicrobial peptides under the influence of vitamin D are LL-37 (cathelicidin) and β-defensin 2, 10,11 which have activity against several bacteria, as well as viruses 12 and fungi. 13 We present here what we believe is currently the largest epidemiological study on adult HSCT patients examining clinical outcome with regards to vitamin D deficiency before HSCT, including both infectious and non-infectious complications.…”

Section: Introductionmentioning

confidence: 99%

Increased incidence of chronic GvHD and CMV disease in patients with vitamin D deficiency before allogeneic stem cell transplantation

Bahr

Blennow

Alm

et al. 2015

Bone Marrow Transplant

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Vitamin D has emerged as a central player in the immune system, with its deficiency being implicated in the pathogenesis of several autoimmune diseases, including chronic GvHD. This is a retrospective cohort analysis of 166 patients, who underwent allogeneic hematopoietic stem cell transplantation (HSCT) at the Karolinska University Hospital, evaluating GvHD, graft failure, infectious complications and survival after HSCT in relation to pre-transplantation vitamin D levels. Most of the patients were deficient in vitamin D before HSCT (median 42 nmol/L). In multivariate analysis, vitamin D level before HSCT was identified as a significant independent risk factor for development of cGvHD. The increased incidence of cGvHD was not coupled to better disease-free survival; instead there was a trend towards lower overall survival in the vitamin D-deficient patients. In addition, we found a significant correlation between vitamin D deficiency and incidence of CMV disease, with no case of CMV disease occurring in patients with sufficient levels of vitamin D before HSCT. Our results support a role of vitamin D in immune tolerance following HSCT. These findings could be highly relevant for the care of HSCT patients, and prospective, randomized studies on the effect of vitamin D supplementation are therefore needed.

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Section: Introductionmentioning

confidence: 99%

Increased incidence of chronic GvHD and CMV disease in patients with vitamin D deficiency before allogeneic stem cell transplantation

Bahr

Blennow

Alm

et al. 2015

Bone Marrow Transplant

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“…The ability of LL-37 alone to modulate inflammatory responses was known to be dependent on the cell type and its TLR expression profile (1,36,37). Poly(I:C)-induced activation of macrophages, dendritic cells, and microglial cells was attenuated by LL-37 (1), whereas LL-37 and poly(I:C) co-stimulation synergistically up-regulate IFN-␤ in keratinocytes (38) and IL-8 and IL-6 in bronchial epithelial cells (39).…”

Section: Discussionmentioning

confidence: 99%

Non-coding Double-stranded RNA and Antimicrobial Peptide LL-37 Induce Growth Factor Expression from Keratinocytes and Endothelial Cells

Adase

Borkowski

Zhang

et al. 2016

Journal of Biological Chemistry

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A critical function for skin is that when damaged it must simultaneously identify the nature of the injury, repair barrier function, and limit the intrusion of pathogenic organisms. These needs are carried out through the detection of damageassociated molecular patterns (DAMPs) and a response that includes secretion of cytokines, chemokines, growth factors, and antimicrobial peptides (AMPs). In this study, we analyzed how non-coding double-stranded RNA (dsRNAs) act as a DAMP in the skin and how the human cathelicidin AMP LL-37 might influence growth factor production in response to this DAMP. dsRNA alone significantly increased the expression of multiple growth factors in keratinocytes, endothelial cells, and fibroblasts. Furthermore, RNA sequencing transcriptome analysis found that multiple growth factors increase when cells are exposed to both LL-37 and dsRNA, a condition that mimics normal wounding. Quantitative PCR and/or ELISA validated that growth factors expressed by keratinocytes in these conditions included, but were not limited to, basic fibroblast growth factor (FGF2), heparin-binding EGF-like growth factor (HBEGF), vascular endothelial growth factor C (VEGFC), betacellulin (BTC), EGF, epiregulin (EREG), and other members of the transforming growth factor ␤ superfamily. These results identify a novel role for DAMPs and AMPs in the stimulation of repair and highlight the complex interactions involved in the wound environment.

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“…LL-37, a 37-residue mature antimicrobial peptide with two leucine residues, is a 37 amino acid peptide derived from human cathelicidin, a cationic antimicrobial peptide of 18-kDa (CAP18). The peptide is mainly produced by epithelial cells and neutrophils [29] and detected in GCF [30]. Human β-defensin-2 (hBD-2), an antimicrobial peptide of the β-defensin family, is induced by gingipains through PAR-2 in gingival epithelial cells [31].…”

Section: Future Prospects: Possible Roles Of Il-33 In Gingival Epithementioning

confidence: 99%

Possible Roles of IL-33 in Periodontal Diseases: Porphyromonas gingivalis Induced IL-33 in Human Gingival Epithelial Cells

Tada

Shimauchi

Takada

et al. 2015

Interface Oral Health Science 2014

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In the oral mucosa, epithelial cells work not only as a physical barrier to pathogens, but also play a pivotal role in initiating immune responses to microbes. Interleukin (IL)-33, a member of the IL-1 family, is constitutively expressed in epithelial cells and amplifies Th2-type inflammatory immune responses. We found that IL-33 was detected in the inflamed gingival epithelium from chronic periodontitis patients, and periodontopathic Porphyromonas gingivalis strongly increased expressions of IL-33 mRNA and molecules in human gingival epithelial cells. In contrast, fimbriae, a lipopeptide and lipopolysaccharide derived from P. gingivalis were not active in this respect. Protease inhibitors specific for gingipains efficiently inhibited the induction of IL-33 mRNA by stimulation with P. gingivalis. Furthermore, P. gingivalis KDP136, a gingipains-null mutant, did not increase IL-33 mRNA expression. We also demonstrated that P. gingivalis upregulated IL-33 mRNA expression through protease-activated receptor-2, phospholipase C, mitogen-activated protein kinase p38 and NF-κB. IL-33 is suggested to negatively regulate antimicrobial peptide LL-37, resulting in attenuation of innate immune responses of gingival epithelial cells in chronic periodontitis. Possible roles of IL-33 in inflammation in the oral mucosa are discussed.

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A comprehensive summary of LL-37, the factotum human cathelicidin peptide

Cited by 479 publications

References 183 publications

Increased incidence of chronic GvHD and CMV disease in patients with vitamin D deficiency before allogeneic stem cell transplantation

Increased incidence of chronic GvHD and CMV disease in patients with vitamin D deficiency before allogeneic stem cell transplantation

Non-coding Double-stranded RNA and Antimicrobial Peptide LL-37 Induce Growth Factor Expression from Keratinocytes and Endothelial Cells

Possible Roles of IL-33 in Periodontal Diseases: Porphyromonas gingivalis Induced IL-33 in Human Gingival Epithelial Cells

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