IL-13 induces expression of CD36 in human monocytes through PPARγ activation

The class B scavenger receptor CD36 is a component of the pattern recognition receptors on monocytes that recognizes a variety of molecules. CD36 expression in monocytes depends on exposure to soluble mediators. We demonstrate here that CD36 expression is induced in human monocytes following exposure to IL-13, a Th2 cytokine, via the peroxisome proliferator-activated receptor (PPAR)gamma pathway. Induction of CD36 protein was paralleled by an increase in CD36 mRNA. The PPAR gamma pathway was demonstrated using transfection of a PPAR gamma expression plasmid into the murine macrophage cell line RAW264.7, expressing very low levels of PPAR gamma, and in peritoneal macrophages from PPAR gamma-conditional null mice. We also show that CD36 induction by IL-13 via PPAR gamma is dependent on phospholipase A2 activation and that IL-13 induces the production of endogenous 15-deoxy-Delta(12,14) -prostaglandin J(2), an endogenous PPAR gamma ligand, and its nuclear localization in human monocytes. Finally, we demonstrate that CD36 and PPAR gamma are involved in IL-13-mediated phagocytosis of Plasmodium falciparum-parasitized erythrocytes. These results reveal a novel role for PPAR gamma in the alternative activation of monocytes by IL-13, suggesting that endogenous PPAR gamma ligands, produced by phospholipase A2 activation, could contribute to the biochemical and cellular functions of CD36.