Transforming growth factor-β1 (TGF-β1) and TGF-β2 decrease expression of CD36, the type B scavenger receptor, through mitogen-activated protein kinase phosphorylation of peroxisome proliferator-activated receptor-γ

CD36, the macrophage type B scavenger receptor, binds and internalizes oxidized low density lipoprotein, a hey event in the development of macrophage foam cells within atherosclerotic lesions. Expression of CD36 in monocyte/macrophages is dependent on differentiation status and exposure to soluble mediators. In this study, we investigated the effect of transforming growth factor-beta 1 (TGF-beta 1) and TGF-beta 2 on the expression of CD36 in macrophages, Treatment of phorbol ester-differentiated THP-1 macrophages with TGF-beta 1 or TGF-beta 2 significantly decreased expression of CD36 mRNA and surface protein. TGF-beta 1/TGF-beta 2 also inhibited CD36 mRNA expression induced by oxidized low density lipoprotein and 15-deoxy Delta(12,14) prostaglandin J(2), a peroxisome proliferator-activated receptor (PPAR)-gamma ligand, suggesting that the TGF-beta 1/TGF-beta 2 down-regulated CD36 expression by inactivating PPAR-gamma-mediated signaling. TGF-beta 1/TGF-beta 2 increased phosphorylation of both mitogen-activated protein (MAP) kinase and PPAR-gamma, whereas NAP kinase inhibitors reversed suppression of CD36 wand inhibited PPAR-gamma phosphorylation induced by TGF-beta 1/TGF-beta 2. Finally, MAP kinase inhibitors alone increased expression of CD36 mRNA and surface protein but had no effect on PPAR-gamma protein levels, Our data demonstrate for the first time that TGF-beta 1 and TGF-beta 2 decrease expression of CD36 by a mechanism involving phosphorylation of MAP kinase, subsequent MAP kinase phosphorylation of PPAR-gamma, and a decrease in CD36 gene transcription by phosphorylated PPAR-gamma.