Inflammatory cytokines induce the transformation of human dermal microvascular endothelial cells into myofibroblasts: a potential role in skin fibrogenesis.
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-1beta (IL-1beta) or tumour necrosis factor-alpha (TNF-alpha), and the transformed cells were characterized by electron microscopy, immunohistochemistry and quantitative RT-PCR.


RESULTS
After short-term exposure to IL-1beta or TNF-alpha (<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 alpha-smooth muscle actin, type I collagen and calponin, and by quantitative RT-PCR gene expression of type I collagen and alpha-smooth muscle actin.


CONCLUSIONS
Long-term exposure to TNF-alpha or IL-1beta 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.
Chaudhuri
V
V
Department of Dermatology, Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Zhou
L
L
Karasek
M
M
D000199:Actins / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics; D020405:Dermis / Q000098:blood supply*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005355:Fibrosis / Q000139:chemically induced / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation; D008840:Microfilament Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000096985:Calponins
D000199:Actins; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D024042:Collagen Type I; D053583:Interleukin-1beta; D008840:Microfilament Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000096985:Calponins