Injury-induced innate immune response in human skin mediated by transactivation of the epidermal growth factor receptor

Sørensen, Ole E.; Thapa, Dharma R.; Roupé, K. Markus; Valore, Erika V.; Sjöbring, Ulf; Roberts, Alice A.; Schmidtchen, Artur; Ganz, Tomas

doi:10.1172/jci28422

Cited by 139 publications

(138 citation statements)

References 43 publications

(52 reference statements)

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“…These studies on the increase of human ␤-defensin 2 expression in wound healing are further supported by studies made by Sørensen et al (32,33), who found that the growth factors important in wound healing, insulinlike growth factor I and TGF-␣, induce the expression of several antimicrobial peptides/polypeptides in human keratinocytes such as human cationic antimicrobial protein hCAP-18/LL-37, human ␤-defensin 3, neutrophil-gelatinase-associated lipocalin, and secretory leukocyte protease inhibitor, defining a host defense role for growth factors in wound healing. Thus, in the case of skin injury, both extracellular matrix components and growth factors may contribute to the production of an array of protective antimicrobial peptides.…”

Section: Discussionsupporting

confidence: 56%

Low Molecular Weight Hyaluronic Acid Increases the Self-Defense of Skin Epithelium by Induction of β-Defensin 2 via TLR2 and TLR4

Gariboldi

Palazzo

Zanobbio

et al. 2008

The Journal of Immunology

157

125

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In sites of inflammation or tissue injury, hyaluronic acid (HA), ubiquitous in the extracellular matrix, is broken down into low m.w. HA (LMW-HA) fragments that have been reported to activate immunocompetent cells. We found that LMW-HA induces activation of keratinocytes, which respond by producing β-defensin 2. This production is mediated by TLR2 and TLR4 activation and involves a c-Fos-mediated, protein kinase C-dependent signaling pathway. LMW-HA-induced activation of keratinocytes seems not to be accompanied by an inflammatory response, because no production of IL-8, TNF-α, IL-1β, or IL-6 was observed. Ex vivo and in vivo treatments of murine skin with LMW-HA showed a release of mouse β-defensin 2 in all layers of the epidermal compartment. Therefore, the breakdown of extracellular matrix components, for example after injury, stimulates keratinocytes to release β-defensin 2, which protects cutaneous tissue at a time when it is particularly vulnerable to infection. In addition, our observation might be important to open new perspectives in the development of possible topical products containing LMW-HA to improve the release of β-defensins by keratinocytes, thus ameliorating the self-defense of the skin for the protection of cutaneous tissue from infection by microorganisms.

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Section: Discussionsupporting

confidence: 56%

Low Molecular Weight Hyaluronic Acid Increases the Self-Defense of Skin Epithelium by Induction of β-Defensin 2 via TLR2 and TLR4

Gariboldi

Palazzo

Zanobbio

et al. 2008

The Journal of Immunology

157

125

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“…The growth factor TGF␣ has been shown to induce AMP expression in keratinocytes (45), whereas HBEGF was shown to stimulate EGFR, leading to the induction of antimicrobial peptides (46). When coupled with our results of synergy between dsRNA and LL-37 leading to growth factor production, we can envision a positive feedback loop.…”

Section: Discussionmentioning

confidence: 54%

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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“…Il en est certainement de même dans la peau des mammifères où une piqûre stérile provoque l'induction d'AMP [41].…”

Section: Revuesunclassified

Mécanismes de défense du nématodeC. elegans

Ziegler

Pujol

2009

Med Sci (Paris)

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Injury-induced innate immune response in human skin mediated by transactivation of the epidermal growth factor receptor

Cited by 139 publications

References 43 publications

Low Molecular Weight Hyaluronic Acid Increases the Self-Defense of Skin Epithelium by Induction of β-Defensin 2 via TLR2 and TLR4

Low Molecular Weight Hyaluronic Acid Increases the Self-Defense of Skin Epithelium by Induction of β-Defensin 2 via TLR2 and TLR4

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

Mécanismes de défense du nématodeC. elegans

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