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

Cell Communication and Signaling

Research

Ruud A Bank¹  Martin Schipper¹  Diana TA Ploeger¹  Nynke A Hosper¹  Saskia de Rond¹  Jasper A Koerts¹ 

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

关键词: Cell plasticity;    Classically/alternatively activated macrophages;    Extracellular matrix remodeling;    Inflammation;    Matrix metalloproteinases;    Paracrine signaling;    Primary human dermal fibroblasts;   

DOI  :  10.1186/1478-811X-11-29

 received in 2012-11-07, accepted in 2013-04-11,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundMacrophages 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).ResultsHDFs 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-conditioned media, the inflammatory markers as well as MMPs and upregulated their collagen production.ConclusionsParacrine factors of M1 or M2 polarized macrophages induced different phenotypes of HDFs and the HDF phenotypes can in turn be reversed, pointing to a high dynamic plasticity of fibroblasts in the different phases of tissue repair.

【 授权许可】

CC BY   
© Ploeger et al.; licensee BioMed Central Ltd. 2013