Ppar-Gamma Ligands Modulate Growth Factor And Bacteria Induced Cellular Responses In Prostate Carcinoma Cells

Prostate carcinoma cells (PC3, LNCAP, DU145) as well as prostate hyperplasia (BPH cells) can be activated for proinflammatory mediator release and parameters of innate immunity by bacteria as well as by various growth factors. Peroxisome proliferator‐activated receptors (PPAR) are ligand activated transcription factors with antiinflammatory, antineoplastic effects on tumor cell proliferation and angiogenesis. The effect of 15d‐PGJ2, and glitazones was analyzed on various prostate carcinoma cells which were stimulated with either VEGF, EGF, HGF, IGF, TNF, SEB, C5a for 5‐ to 48 hours. As bacterial stimuli were chosen Staph. aureus (n=5) or E. col i (n=5). The release of IL‐6, IL‐8, PGE2, TGFβ was studied by Elisa, by RT‐PCR and Taqman analysis the expression of p22‐, 47‐, 67‐phox, gp91‐phox, cysteinylleukotriene receptors 1, 2, trefoil peptides (TFF1‐3), protease activated receptors (PAR1‐4), toll‐like receptors (TLR2, 4, 9), cyclooxygenase 2. We show: PPARγ‐ligands 1.) interact differently with carcinoma cells for mediator release as well as cell surface receptor expression and 2.) differences in pro‐ and antiinflammatory responses depend on the individual cell as well as the stimulus via differences in signal transduction. The results suggest a potential use of PPARγ‐ligands as adjuvant therapy of prostate carcinoma and further one has to consider the individual cell type and mode of cellular activation.