title: Peroxisome proliferator activated receptor-α agonists suppress transforming growth factor-α-induced matrix metalloproteinase-9 expression in human keratinocytes.
abstract: The peroxisome proliferator-activated receptors (PPARs), PPARα, PPARδ, and PPARγ, are nuclear ligand-activated transcription factors that are best known as regulators of glucose and lipid metabolism. PPARα agonists have been shown to have profound anti-inflammatory and antiproliferative effects on human keratinocytes, and are important for maintaining homeostasis of the skin. To better characterize the mechanisms underlying these phenomena, we analysed the effects of PPARα agonists on transforming growth factor (TGF)-α-induced expression of matrix metalloproteinase (MMP)-9. MMP-9 expression in keratinocytes has previously been linked to inflammatory skin diseases, regenerative skin mechanisms, and tumour development and metastasis. We found that PPARα agonists effectively inhibited TGF-α-induced MMP-9 expression in human keratinocytes via a post-transcriptional mechanism, revealing a novel and important aspect of the anti-inflammatory and anticarcinogenic action of these compounds.
authors.affiliation: Department of Dermatology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany. markus.meissner@kgu.de
authors.forename: M
authors.initials: M
authors.lastname: Meissner
authors.forename: B
authors.initials: B
authors.lastname: Berlinski
authors.forename: J
authors.initials: J
authors.lastname: Gille
authors.forename: M
authors.initials: M
authors.lastname: Doll
authors.forename: R
authors.initials: R
authors.lastname: Kaufmann
mesh_terms: D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D047493:PPAR alpha / Q000819:agonists*; D016133:Polymerase Chain Reaction; D016211:Transforming Growth Factor alpha / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D047493:PPAR alpha; D016211:Transforming Growth Factor alpha; D020780:Matrix Metalloproteinase 9