The Modulatory Effect of 15d-PGJ2 in Dendritic Cells

Abstract

The PPAR-γ ligands, in special 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2), negatively regulate the cells of innate and adaptative immune system and present excellent results in different models of inflammatory diseases. These findings support the notion that PPAR-γ ligands may be used as therapeutic agents in different diseases. Although PPAR-γ is expressed in different cells and tissues including dendritic cells (DC), few studies have evaluated the effects of these ligands on DCs. Thus, in this study we evaluated the effect of 15d-PGJ2 on DC surface molecule expression, including MHC-II, CD80, and CD86. In addition, we quantified cytokine production in the presence of 15d-PGJ2 or rosiglitazone. Expression of the surface molecules was measured by flow cytometry and cytokines production was measured by ELISA in supernatant of BMDC cultures. The results suggest that 15d-PGJ2 reduced the expression of costimulatory molecules (CD80 and CD86), without altering MCH-class II expression. Furthermore the natural PPAR-γ agonist significantly reduced levels of proinflammatory cytokines (IL-12, IFN-γ, and TNF-α) and appears to also reduce IL-1β levels. Rosiglitazone reduced the expression of these cytokines albeit to a lesser extent. These data suggest the idea that 15d-PGJ2 could be a therapeutic strategy in diseases where DCs play a crucial role, due to its ability to reduce costimulatory molecules expression and modulate the inflammatory environment.