Peroxisome Proliferator-activator Receptor-?× and its ligands can attenuate biological functions of human natural killer cells

ZHANG X; RODRIGUEZ GALAN MC; SUBLESKI J; ORTALDO J; HODGE D; WANG JM; SCHIMATAZO O; REYNOLDS D; YOUNG HA

AMER SOC HEMATOLOGY

Año: 2004 vol. 104 p. 3276 - 3276

nterferon-gamma (IFN-gamma) production and cytolytic activity are 2 major biologic functions of natural killer (NK) cells that are important for innate immunity. We demonstrate here that these functions are compromised in human NK cells treated with peroxisome proliferator?activated-gamma (PPAR-gamma) ligands via both PPAR-gamma?dependent and -independent pathways due to variation in PPAR-gamma expression. In PPAR-gamma?null NK cells,  15-deoxy-12,14 prostaglandin J2 (15d-PGJ2), a natural PPAR-gamma ligand, reduces IFN-gamma production that can be reversed by MG132 and/or chloroquine, and it inhibits cytolytic activity of NK cells through reduction of both conjugate formation and CD69 expres-sion. In PPAR-gamma?positive NK cells, PPAR-gamma activation by 15d-PGJ2 and ciglitazone(a synthetic ligand) leads to reduction in both mRNA and protein levels of IFN-gamma.Overexpression of PPAR-gamma in PPAR-gamma null NK cells reduces IFN-gamma gene expression. However,