Article: article from journal or magazin.
Regulation of epithelial-mesenchymal IL-1 signaling by PPARbeta/delta is essential for skin homeostasis and wound healing.
Journal of Cell Biology
Skin morphogenesis, maintenance, and healing after wounding require complex epithelial-mesenchymal interactions. In this study, we show that for skin homeostasis, interleukin-1 (IL-1) produced by keratinocytes activates peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) expression in underlying fibroblasts, which in turn inhibits the mitotic activity of keratinocytes via inhibition of the IL-1 signaling pathway. In fact, PPARbeta/delta stimulates production of the secreted IL-1 receptor antagonist, which leads to an autocrine decrease in IL-1 signaling pathways and consequently decreases production of secreted mitogenic factors by the fibroblasts. This fibroblast PPARbeta/delta regulation of the IL-1 signaling is required for proper wound healing and can regulate tumor as well as normal human keratinocyte cell proliferation. Together, these findings provide evidence for a novel homeostatic control of keratinocyte proliferation and differentiation mediated via PPARbeta/delta regulation in dermal fibroblasts of IL-1 signaling. Given the ubiquitous expression of PPARbeta/delta, other epithelial-mesenchymal interactions may also be regulated in a similar manner.
Animals, Autocrine Communication, Cell Differentiation, Cell Proliferation, Cells, Cultured, Cytokines/metabolism, Epithelial Cells/enzymology, Epithelial Cells/immunology, Fibroblasts/enzymology, Fibroblasts/immunology, Gene Knockdown Techniques, Homeostasis, Humans, Intercellular Signaling Peptides and Proteins/metabolism, Interleukin 1 Receptor Antagonist Protein/genetics, Interleukin 1 Receptor Antagonist Protein/metabolism, Interleukin-1/genetics, Interleukin-1/metabolism, Interleukin-1alpha/metabolism, Interleukin-1beta/metabolism, MAP Kinase Kinase Kinases/metabolism, Mice, Mice, Knockout, Organ Culture Techniques, PPAR delta/deficiency, PPAR delta/genetics, PPAR-beta/deficiency, PPAR-beta/genetics, Paracrine Communication, Promoter Regions, Genetic, RNA Interference, Signal Transduction, Skin/enzymology, Skin/immunology, Time Factors, Transcription Factor AP-1/metabolism, Transcriptional Activation, Wound Healing
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