ECE2010 Poster Presentations Signal transduction (6 abstracts)
Peroxisome-proliferator-activated receptor gamma is required for modulating endothelial inflammatory response through a novel nongenomic mechanism
Giulia Cantini , Adriana Lombardi , Elisa Borgogni , Michela Francalanci , Elisabetta Ceni , Stefania Gelmini , Giada Poli , Andrea Galli , Mario Serio , Gianni Forti & Michaela Luconi
Department of Cinical Physiopathology, University of Florence, Florence, Italy.
Besides their well-known anti-diabetic effects, the peroxisome proliferator-activated receptor γ (PPARγ) thiazolidinedione ligands (TZD) have been suggested to also display anti-inflammatory properties. The receptor role in mediating such effects is far from being elucidated. Here, we demonstrate that PPARγ is necessary for TZD to interfere with TNFα and IFNγ inflammatory activity in human endothelial cells. Different PPARγ ligands similarly inhibit cytokinic stimulation of IFNγ-inducible-protein-of-10-kDa (IP-10) secretion in a dose-dependent manner and prevent the induced phosphorylation/activation of extracellular-signaling-regulated-kinases (ERK1/2). To further confirm the role of PPARγ in mediating both rapid and long term anti-inflammatory effects of its ligands, we evaluated RGZ inhibitory action in PPARγ-silenced and – overexpressing cells. PPARγ-silencing results in a reversion of RGZ inhibitory activity on cyto/chemokines secretion and rapid ERK phosphorylation. Conversely, receptor-overexpression significantly increases RGZ inhibitory activity. Finally, PPARγ-overexpression results in reduction of ERK1/2 phosphorylation and inflammatory secretions in response to TNFα and IFNγ even in the absence of RGZ, suggesting a restraining effect controlled by endogenous ligands.
In conclusion, our data provide the first evidence that PPARγ is involved in the TZD anti-inflammatory action in endothelial cells, not only by modulating cyto/chemokine secretions but also by restraining ERK activation through a novel rapid nongenomic mechanism.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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