Objective: CD36 is a receptor, whose expression increases during the differentiation of monocytes to macrophages, playing a key role in the phagocytosis of apoptotic cells and in the formation of foam cells during atherosclerosis. Recently, it has been described that ligands of PPARgamma induce CD36 expression and inhibit cyclooxygenase expression in macrophages. Our aim was to study whether the reduction of endogenous prostaglandin production could modify CD36 expression in macrophages and to outline the potential mechanism.
Methods and results: CD36 expression was measured by flow cytometry in THP-1 cells differentiated to macrophages that had been incubated with aspirin (ASA) alone or in combination with PGE(2), sulprostone (EP1/EP3 agonist), butaprost (EP2 agonist,) and PGE1 alcohol (EP2/EP4 agonist). Aspirin induced CD36 expression. Only PGE(2) and PGE1 alcohol completely abolished CD36 induction by aspirin, whereas butaprost strongly reduced it. BADGE (a PPARgamma antagonist) or diclofenac (a PPARgamma antagonist and a cyclooxygenase inhibitor) in aspirin-incubated cells did not reduce CD36 induction. On the other hand, aspirin also induced the expression of SR-BI and ABCA1, an HDL receptor and an HDL formation-related protein, respectively.
Conclusions: Aspirin produces an increase of CD36 expression in THP-1 macrophages by a PGE(2)-dependent mechanism. The PGE(2) receptors implicated in CD36 modulation by ASA are the EP2/EP4 subtypes. Further, we provide evidence of SR-BI and ABCA1 induction by aspirin treatment.