Aspirin increases CD36, SR-BI, and ABCA1 expression in human THP-1 macrophages.
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.


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.
Viñals
Marisa
M
Unitat de Farmacologia, Facultat de Farmacia, Universitat de Barcelona, Nucli Universitari de Pedralbes, E-08028 Barcelona, Spain. mvinals@lloguerspous.com
Bermúdez
Ignacio
I
Llaverias
Gemma
G
Alegret
Marta
M
Sanchez
Rosa Maria
RM
Vázquez-Carrera
Manuel
M
Laguna
Juan Carlos
JC
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D015153:Blotting, Western / Q000379:methods; D018955:CD36 Antigens / Q000276:immunology*; D002460:Cell Line; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists; D047495:PPAR gamma / Q000819:agonists; D048068:PPAR-beta / Q000819:agonists; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000378:metabolism*; D051116:Receptors, Scavenger; D013997:Time Factors
C477819:15-deoxyprostaglandin J2; C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018955:CD36 Antigens; D047493:PPAR alpha; D047495:PPAR gamma; D048068:PPAR-beta; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D011464:Epoprostenol; D015232:Dinoprostone; D001241:Aspirin; D015230:Prostaglandin D2