Inflammatory cytokines induce the transformation of human dermal microvascular endothelial cells into myofibroblasts: A potential role in skin fibrogenesis

Abstract

Background: The myofibroblast plays a central role in wound contraction and in the pathology of fibrosis. The origin(s) of this important cell type in skin has not been firmly established. Methods: Human epithelioid dermal microvascular endothelial cells (HDMEC) were isolated from foreskin tissue and maintained in cell culture. The transformation of epithelioid HDMEC into myofibroblasts (EMT) was induced by the inflammatory cytokines interleukin-1β (IL-1β) or tumour necrosis factor-α (TNF-α), and the transformed cells were characterized by electron microscopy, immunohistochemistry and quantitative RT-PCR. Results: After short-term exposure to IL-1β or TNF-α (<3 days), EMT was reversible; after long-term exposure (>10 days), EMT was permanent. The transformed cells were identified as myofibroblasts by cytoplasmic microfilaments with dense bodies and attachment plaques, by the expression of α-smooth muscle actin, type I collagen and calponin, and by quantitative RT-PCR gene expression of type I collagen and α-smooth muscle actin. Conclusions: Long-term exposure to TNF-α or IL-1β induced the permanent transformation of HDMEC into myofibroblasts in cell culture. A similar transformation following chronic inflammatory stimulation in vivo may explain one source of myofibroblasts in skin fibrogenesis. © Blackwell Munksgaard 2006.