Biphasic expression of stromal cell-derived factor-1 during human wound healing.

Abstract

Chemokines tightly regulate the spatial and temporal infiltration of invading leucocyte subsets during wound healing. Stromal cell-derived factor-1 (SDF-1/CXCL12) is a homeostatic chemokine with multiple functions; its role during cutaneous wound healing, however, needs to be explored. To elucidate expression of the multifunctional CXC chemokine SDF-1/CXCL12 during human wound healing. Skin biopsies were obtained from 14 volunteers between 1 and 21 days after incisional wounding and processed for in situ hybridization and immunohistochemistry. We analysed the spatial and temporal distribution of SDF-1/CXCL12 after artificial wounding and detected a complete downregulation at both the mRNA and the protein level within the fibrous stroma that replaces the initial wound defect. However, increased levels of SDF-1/CXCL12 were observed at the wound margins. Focusing on mediators regulating SDF-1/CXCL12 expression in vitro we realized that both tumour necrosis factor-alpha and interferon-gamma downregulated its expression in human dermal microvascular endothelial cells and fibroblasts. Our data suggest that SDF-1/CXCL12 is tightly regulated during wound repair. Increased expression at the wound margin may contribute to the accumulation of endothelial progenitor cells, thus accelerating neovascularization.