IL-13 induces expression of CD36 in human monocytes through PPARgamma 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 PPARgamma pathway was demonstrated using transfection of a PPARgamma expression plasmid into the murine macrophage cell line RAW264.7, expressing very low levels of PPARgamma, and in peritoneal macrophages from PPARgamma-conditional null mice. We also show that CD36 induction by IL-13 via PPARgamma is dependent on phospholipase A2 activation and that IL-13 induces the production of endogenous 15-deoxy-Delta12,14-prostaglandin J2, an endogenous PPARgamma ligand, and its nuclear localization in human monocytes. Finally, we demonstrate that CD36 and PPARgamma are involved in IL-13-mediated phagocytosis of Plasmodium falciparum-parasitized erythrocytes. These results reveal a novel role for PPARgamma in the alternative activation of monocytes by IL-13, suggesting that endogenous PPARgamma ligands, produced by phospholipase A2 activation, could contribute to the biochemical and cellular functions of CD36.
Berry
Antoine
A
Macrophages, Mediateurs de l'Inflammation et Interactions Cellulaires, Université Paul Sabatier Toulouse III, INSERM IFR 31, Toulouse, France. berry.a@chu-toulouse.fr
Balard
Patricia
P
Coste
Agnès
A
Olagnier
David
D
Lagane
Céline
C
Authier
Hélène
H
Benoit-Vical
Françoise
F
Lepert
Jean-Claude
JC
Séguéla
Jean-Paul
JP
Magnaval
Jean-François
JF
Chambon
Pierre
P
Metzger
Daniel
D
Desvergne
Béatrice
B
Wahli
Walter
W
Auwerx
Johan
J
Pipy
Bernard
B
D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D063065:Organophosphonates / Q000494:pharmacology; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D010963:Plasmodium falciparum / Q000502:physiology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014162:Transfection
C477819:15-deoxyprostaglandin J2; C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D001095:Arachidonic Acids; D018955:CD36 Antigens; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D018793:Interleukin-13; D063065:Organophosphonates; D047495:PPAR gamma; D045162:Thiazolidinediones; C104810:methyl arachidonylfluorophosphonate; D000077154:Rosiglitazone; D004247:DNA; D010741:Phospholipases A; D054467:Phospholipases A2; D015230:Prostaglandin D2