Cell plasticity in wound healing: paracrine factors of M1/ M2 polarized macrophages influence the phenotypical state of

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Cell plasticity in wound healing: paracrine factors of M1/ M2 polarized macrophages influence the phenotypical state of dermal fibroblasts Cell Communication and Signaling 2013, 11:29

doi:10.1186/1478-811X-11-29

Diana TA Ploeger ([email protected]) Nynke A Hosper ([email protected]) Martin Schipper ([email protected]) Jasper A Koerts ([email protected]) Saskia de Rond ([email protected]) Ruud A Bank ([email protected])

ISSN Article type

1478-811X Research

Submission date

7 November 2012

Acceptance date

11 April 2013

Publication date

19 April 2013

Article URL

http://www.biosignaling.com/content/11/1/29

This peer-reviewed article can be downloaded, printed and distributed freely for any purposes (see copyright notice below). Articles in CCS are listed in PubMed and archived at PubMed Central. For information about publishing your research in CCS or any BioMed Central journal, go to http://www.biosignaling.com/authors/instructions/ For information about other BioMed Central publications go to http://www.biomedcentral.com/

© 2013 Ploeger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Cell plasticity in wound healing: paracrine factors of M1/ M2 polarized macrophages influence the phenotypical state of dermal fibroblasts Diana TA Ploeger1*,† * Corresponding author Email: [email protected] Nynke A Hosper1,† Email: [email protected] Martin Schipper1 Email: [email protected] Jasper A Koerts1 Email: [email protected] Saskia de Rond1 Email: [email protected] Ruud A Bank1 Email: [email protected] 1

Department of Pathology and Medical Biology, Medical Biology Section, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen 9713 GZ, The Netherlands †

Equal contributors.

Abstract Background Macrophages and fibroblasts are two major players in tissue repair and fibrosis. Despite the relevance of macrophages and fibroblasts in tissue homeostasis, remarkably little is known whether macrophages are able to influence the properties of fibroblasts. Here we investigated the role of paracrine factors secreted by classically activated (M1) and alternatively activated (M2) human macrophages on human dermal fibroblasts (HDFs).

Results HDFs stimulated with paracrine factors from M1 macrophages showed a 10 to > 100-fold increase in the expression of the inflammatory cytokines IL6, CCL2 and CCL7 and the matrix metalloproteinases MMP1 and MMP3. This indicates that factors produced by M1 macrophages induce a fibroblast phenotype with pro-inflammatory and extracellular matrix (ECM) degrading properties. HDFs stimulated with paracrine factors secreted by M2 macrophages displayed an increased proliferation rate. Interestingly, the M1-activated pro-

inflammatory fibroblasts downregulated, after exposure to paracrine factors produced by M2 macrophages or non