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01.12.2018 | Research | Ausgabe 1/2018 Open Access

European Journal of Medical Research 1/2018

Chemokine ligand–receptor interactions critically regulate cutaneous wound healing

Zeitschrift:
European Journal of Medical Research > Ausgabe 1/2018
Autoren:
Erich Bünemann, Norman-Philipp Hoff, Bettina Alexandra Buhren, Ulrike Wiesner, Stephan Meller, Edwin Bölke, Anja Müller-Homey, Robert Kubitza, Thomas Ruzicka, Albert Zlotnik, Bernhard Homey, Peter Arne Gerber
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s40001-017-0299-0) contains supplementary material, which is available to authorized users.
Erich Bünemann and Norman-Philipp Hoff contributed equally to this work
Bernhard Homey and Peter Arne Gerber contributed equally to this work

Abstract

Background

Wound healing represents a dynamic process involving directional migration of different cell types. Chemokines, a family of chemoattractive proteins, have been suggested to be key players in cell-to-cell communication and essential for directed migration of structural cells. Today, the role of the chemokine network in cutaneous wound healing is not fully understood. Unraveling the chemokine-driven communication pathways in this complex process could possibly lead to new therapeutic strategies in wound healing disorders.

Methods

We performed a systematic, comprehensive time-course analysis of the expression and function of a broad variety of cytokines, growth factors, adhesion molecules, matrixmetalloproteinases and chemokines in a murine cutaneous wound healing model.

Results

Strikingly, chemokines were found to be among the most highly regulated genes and their expression was found to coincide with the expression of their matching receptors. Accordingly, we could show that resting and activated human primary keratinocytes (CCR3, CCR4, CCR6, CXCR1, CXCR3), dermal fibroblasts (CCR3, CCR4, CCR10) and dermal microvascular endothelial cells (CCR3, CCR4, CCR6, CCR8, CCR9, CCR10, CXCR1, CXCR2, CXCR3) express a distinct and functionally active repertoire of chemokine receptors. Furthermore, chemokine ligand–receptor interactions markedly improved the wound repair of structural skin cells in vitro.

Conclusion

Taken together, we here present the most comprehensive analysis of mediators critically involved in acute cutaneous wound healing. Our findings suggest therapeutic approaches for the management of wound closure by targeting the chemokine network.
Zusatzmaterial
Additional file 1: Figure S1. Human primary keratinocytes expressing CCR4, CCR6, CCR9, CXCR1 and CXCR3 on their surface. Flow cytometric analysis of chemokine receptor repertoire in cultured human primary keratinocytes. Representative results from one of at least three different donors.
Additional file 2: Figure S2. Human primary dermal fibroblasts expressing CCR3, CCR4 and CCR10 on their surface. Flow cytometric analysis of chemokine receptor repertoire in cultured human primary dermal fibroblasts. Representative results from one of at least three different donors.
Additional file 3: Figure S3. Human primary dermal microvascular endothelial cells expressing CCR3, CCR4, CCR6, CCR8, CCR9, CCR10, CXCR1, CXCR2, CXCR3 and CXCR4 on their surface. Flow cytometric analysis of chemokine receptor repertoire in cultured human primary dermal microvascular endothelial cells. Representative results of one of at least three different donors.
Literatur
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