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

Jihong Han, David P. Hajjar, James M. Tauras, Jianwei Feng, Antonio M. Gotto, Andrew C. Nicholson

Research output: Contribution to journalArticle

157 Scopus citations

Abstract

CD36, the macrophage type B scavenger receptor, binds and internalizes oxidized low density lipoprotein, a key 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-β1 (TGF-β1) and TGF-β2 on the expression of CD36 in macrophages. Treatment of phorbol ester-differentiated THP-1 macrophages with TGF-β1 or TGF-β2 significantly decreased expression of CD36 mRNA and surface protein. TGF-β1/TGF-β2 also inhibited CD36 mRNA expression induced by oxidized low density lipoprotein and 15-deoxyΔ12,14 prostaglandin J2, a peroxisome proliferator-activated receptor (PPAR)-γ ligand, suggesting that the TGF-β1/TGF-β2 down-regulated CD36 expression by inactivating PPAR-γ-mediated signaling. TGF-β1/TGF-β2 increased phosphorylation of both mitogen-activated protein (MAP) kinase and PPAR-γ, whereas MAP kinase inhibitors reversed suppression of CD36 and inhibited PPAR-γ phosphorylation induced by TGF-β1/TGF-β2. Finally, MAP kinase inhibitors alone increased expression of CD36 mRNA and surface protein but had no effect on PPAR-γ protein levels. Our data demonstrate for the first time that TGF-β1 and TGF-β2 decrease expression of CD36 by a mechanism involving phosphorylation of MAP kinase, subsequent MAP kinase phosphorylation of PPAR-γ, and a decrease in CD36 gene transcription by phosphorylated PPAR-γ.

Original languageEnglish (US)
Pages (from-to)1241-1246
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number2
DOIs
StatePublished - Jan 14 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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