PPARγ is not required for the inhibitory actions of PGJ 2 on cytokine signaling in pancreatic β-cells

• Published in: American journal of physiology: endocrinology and metabolism Vol. 286; no. 3; pp. E329 - E336
• Main Authors: Weber, Sarah M., Scarim, Anna L., Corbett, John A.
• Format: Journal Article
• Language: English
• Published: 01.03.2004
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00392.2003

Peroxisome proliferator-activated receptor (PPAR)γ agonists, such as 15-deoxy-Δ 12,14 -prostaglandin J 2 (PGJ 2 ) and troglitazone, have been shown to elicit anti-inflammatory effects in pancreatic β-cells that include inhibition of cytokine-stimulated inducible nitric oxide synthase (iNOS) gene expression and production of nitric oxide. In addition, these ligands impair IL-1-induced NF-κB and MAPK as well as IFN-γ-stimulated signal transducer and activator of transcription (STAT)1 activation in β-cells. The purpose of this study was to determine if PPARγ activation participates in the anti-inflammatory actions of PGJ 2 in β-cells. Pretreatment of RINm5F cells for 6 h with PGJ 2 results in inhibition of IL-1-stimulated IκB degradation and IFN-γ-stimulated STAT1 phosphorylation. Overexpression of a dominant-negative (dn) PPARγ mutant or treatment with the PPARγ antagonist GW-9662 does not modulate the inhibitory actions of PGJ 2 on cytokine signaling in RINm5F cells. Although these agents fail to attenuate the inhibitory actions of PGJ 2 on cytokine signaling, they do inhibit PGJ 2 -stimulated PPARγ response element reporter activity. Consistent with the inability to attenuate the inhibitory actions of PGJ 2 on cytokine signaling, neither dnPPARγ nor GW-9662 prevents the inhibitory actions of PGJ 2 on IL-1-stimulated iNOS gene expression or nitric oxide production by RINm5F cells. These findings support a PPARγ-independent mechanism by which PPARγ ligands impair cytokine signaling and iNOS expression by islets.