In vitro and In vivo Wound Healing-Promoting Activities of Human Cathelicidin LL-37

Carretero, Marta; Escámez, M.J.; García, Marta; Duarte, Blanca; Holguín, Almudena; Retamosa, Luisa; Jorcano, José L.; Río, Marcela Del; Larcher, Fernando

doi:10.1038/sj.jid.5701043

Cited by 294 publications

(266 citation statements)

References 58 publications

(65 reference statements)

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“…As examples, pulmonary surfactant protein D has roles in surfactant lipid homeostasis and some antimicrobial peptides (e.g., LL-37) have roles in wound healing and epithelial barrier function [108,109]. Also, as with other innate defense mediators, there is evidence that extracellular histones can contribute to cell injury, harmful inflammation and activation of thrombosis.…”

Section: Resultsmentioning

confidence: 99%

Histones as Mediators of Host Defense, Inflammation and Thrombosis

et al. 2016

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Histones are known for their ability to bind to and regulate expression of DNA. However, histones are also present in cytoplasm and extracellular fluids where they serve host defense functions and promote inflammatory responses. Histones are a major component of neutrophil extracellular traps that contribute to bacterial killing but also to inflammatory injury. Histones can act as antimicrobial peptides and directly kill bacteria, fungi, parasites and viruses, in vitro and in a variety of animal hosts. In addition, histones can trigger inflammatory responses in some cases acting through Toll-like receptors or inflammasome pathways. Extracellular histones mediate organ injury (lung, liver), sepsis physiology, thrombocytopenia and thrombin generation and some proteins can bind histones and reduce these potentially harmful effects.

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Section: Resultsmentioning

confidence: 99%

Histones as Mediators of Host Defense, Inflammation and Thrombosis

et al. 2016

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“…Additionally, H. pylori induces the production of peptide LL37 (35). This peptide, by activating FPRs, plays an important role in wound healing (36). Furthermore, it is possible that several cytokines, released during chronic inflammation, exert a priming effect on epithelial cells that permits in vivo cellular activation with lower concentrations of Hp (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori Hp(2–20) Promotes Migration and Proliferation of Gastric Epithelial Cells by Interacting with Formyl Peptide Receptors In Vitro and Accelerates Gastric Mucosal Healing In Vivo

Paulis¹,

Prevete²,

Rossi³

et al. 2009

The Journal of Immunology

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Helicobacter pylori-derived peptide RpL1 aa 2–20 (Hp(2–20)) in addition to its antimicrobial action exerts several immunomodulatory effects in eukaryotic cells by interacting with formyl peptide receptors (FPRs). It has recently been shown that activation of FPRs facilitates intestinal epithelial cell restitution. We investigated whether Hp(2–20) induces healing of injured gastric mucosa and assessed the mechanisms underlying any such effect. We investigated the expression of FPRs in two gastric epithelial cell lines (MKN-28 and AGS) at mRNA and protein level. To determine whether FPRs were functional we performed chemotaxis experiments and proliferation assays and studied the Hp(2–20)-activated downstream signaling pathway. The effect of Hp(2–20) on mucosal healing was evaluated in rats after indomethacin-induced injury. Here we show that: (1) FPRs were expressed in both cell lines; (2) Hp(2–20) stimulated migration and proliferation of gastric epithelial cells; (3) this effect was specifically mediated by formyl peptide receptor-like 1 (FPRL1) and FPRL2 and was associated with activation of FPR-related downstream signaling pathways; (4) Hp(2–20) up-regulated the expression and secretion of vascular endothelial growth factor; and (5) Hp(2–20) accelerated healing of rat gastric mucosa after injury brought about by indomethacin at both the macroscopic and microscopic levels. In conclusion, by interacting with FRPL1 and FPRL2, H. pylori-derived Hp(2–20) induces cell migration and proliferation, as well as the expression of vascular endothelial growth factor, thereby promoting gastric mucosal healing. This study provides further evidence of the complexity of the relationship between H. pylori and human gastric mucosa, and it suggests that a bacterial product may be used to heal gastric mucosal injury.

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“…Pertussis toxin was used to demonstrate the involvement of the G icoupled receptor family in the IDR-1002-activity, with possible involvement of the FPRL-1 family member. G i -coupled receptors are known to mediate a range of immunomodulatory functions of natural cathelicidins, including chemotactic activity toward certain cell types (7,8), effects on neutrophil survival (10, 11), keratinocyte proliferation, migration, and wound healing (48), as well as the angiogenic activity on the vascular endothelial cells (49). FRPL-1 is one of the receptors mediating these activities; however, it has not been shown to mediate chemokine induction, and other unknown G i -coupled receptors are required in some cell types (8,10).…”

Section: Discussionmentioning

confidence: 99%

Synthetic Cationic Peptide IDR-1002 Provides Protection against Bacterial Infections through Chemokine Induction and Enhanced Leukocyte Recruitment

Nijnik

Madera

et al. 2010

The Journal of Immunology

182

221

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With the rapid rise in the incidence of multidrug resistant infections, there is substantial interest in host defense peptides as templates for production of new antimicrobial therapeutics. Natural peptides are multifunctional mediators of the innate immune response, with some direct antimicrobial activity and diverse immunomodulatory properties. We have previously developed an innate defense regulator (IDR) 1, with protective activity against bacterial infection mediated entirely through its effects on the immunity of the host, as a novel approach to anti-infective therapy. In this study, an immunomodulatory peptide IDR-1002 was selected from a library of bactenecin derivatives based on its substantially more potent ability to induce chemokines in human PBMCs. The enhanced chemokine induction activity of the peptide in vitro correlated with stronger protective activity in vivo in the Staphylococcus aureus-invasive infection model, with a >5-fold reduction in the protective dose in direct comparison with IDR-1. IDR-1002 also afforded protection against the Gram-negative bacterial pathogen Escherichia coli. Chemokine induction by IDR-1002 was found to be mediated through a Gi-coupled receptor and the PI3K, NF-κB, and MAPK signaling pathways. The protective activity of the peptide was associated with in vivo augmentation of chemokine production and recruitment of neutrophils and monocytes to the site of infection. These results highlight the importance of the chemokine induction activity of host defense peptides and demonstrate that the optimization of the ex vivo chemokine-induction properties of peptides is a promising method for the rational development of immunomodulatory IDR peptides with enhanced anti-infective activity.

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In vitro and In vivo Wound Healing-Promoting Activities of Human Cathelicidin LL-37

Cited by 294 publications

References 58 publications

Histones as Mediators of Host Defense, Inflammation and Thrombosis

Histones as Mediators of Host Defense, Inflammation and Thrombosis

Helicobacter pylori Hp(2–20) Promotes Migration and Proliferation of Gastric Epithelial Cells by Interacting with Formyl Peptide Receptors In Vitro and Accelerates Gastric Mucosal Healing In Vivo

Synthetic Cationic Peptide IDR-1002 Provides Protection against Bacterial Infections through Chemokine Induction and Enhanced Leukocyte Recruitment

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