cytochrome-c-t and 2-2-bis(4-glycidyloxyphenyl)propane

Trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) has been shown to alter immune function. PPARgamma has been shown to potentially play an important role in regulating inflammatory and immune responses by modulating the activity of monocytes and macrophages. Previous studies have indicated that the phagocytic capacity of porcine peripheral blood polymorphonuclear cells (PMN) was enhanced by the culture supernatant fraction from t10c12-CL-stimulated porcine peripheral blood mononuclear cells (PBMC) but not by t10c12-CLA itself. In the present study, we examined the effects of t10c12-CLA on PPARgamma and TNF-alpha expression of porcine PBMC and the phagocytic capacity of PMN. t10c12-CLA increased TNF-alpha mRNA expression and production by PBMC. The phagocytic capacity of porcine PMN was enhanced by either culture supernatant fraction from PBMC treated with t10c12-CLA or recombinant porcine (rp) TNF-alpha. Anti-rpTNF-alpha polyclonal antibody inhibited the enhancement of PMN phagocytic capacity. t10c12-CLA also up regulated PPARgamma mRNA expression in porcine PBMC. Bisphenol A diglycidyl ether, a PPARgamma antagonist, not only completely negated the t10c12-CLA-stimulating effects on TNF-alpha expression and production by porcine PBMC, but also decreased the enhancement of PMN phagocytic capacity by the t10c12-CLA-stimulated porcine PBMC culture supernatant fraction. These results suggest that t10c12-CLA has an immunostimulating effect on porcine PMN phagocytic capacity, which is mediated by TNF-alpha from PBMC via a PPARgamma-dependent pathway.

Topics: Animals; Benzhydryl Compounds; Cells, Cultured; Cytochromes c; Epoxy Compounds; Flow Cytometry; Linoleic Acids, Conjugated; Neutrophils; Phagocytosis; PPAR gamma; Reverse Transcriptase Polymerase Chain Reaction; RNA; Swine; Tumor Necrosis Factor-alpha

(1) Bisphenol A diglycidyl ether (BADGE) is a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) antagonist, which is able to induce apoptosis in tumor cells independently of PPAR-gamma in caspase-dependent and -independent manners. Additionally, BADGE promotes TRAIL-induced apoptosis. (2) We report that BADGE activates via Bax and caspases-2 and -8 both the intrinsic and extrinsic apoptotic pathways using Bid as a shunt. (3) BADGE stimulates the mitochondrial release of apoptosis-inducing factor (AIF), cytochrome c and second mitochondria-derived activator of caspase/direct IAP-binding protein with low pl (Smac/DIABLO). The release of cytochrome c could not be blocked by inhibitors of caspases-3, -8 and -9 indicating that BADGE acts upstream of caspases-3 and -9 and does not involve caspase-8 to release cytochrome c. (4) While the caspase-independent apoptotic effect might be mediated by AIF, the sensitizing effect of BADGE against other apoptotic substances is most likely mediated by the X-linked inhibitor of apoptosis inhibitor Smac/DIABLO. (5) Our data suggest that BADGE or BADGE derivatives could represent promising substances for the treatment of neoplasms improving the antitumoral activity of TRAIL.

Topics: Apoptosis; Apoptosis Inducing Factor; Apoptosis Regulatory Proteins; bcl-2-Associated X Protein; Benzhydryl Compounds; BH3 Interacting Domain Death Agonist Protein; Carrier Proteins; Cytochromes c; Enzyme Inhibitors; Epoxy Compounds; Flavoproteins; Humans; Intracellular Signaling Peptides and Proteins; Jurkat Cells; Membrane Proteins; Mitochondria; Mitochondrial Proteins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2