Adipocyte fatty acid-binding protein expression and lipid accumulation are increased during activation of murine macrophages by toll-like receptor agonists.
OBJECTIVE
Toll-like receptors (TLRs) recognize pathogens and mediate signaling pathways important for host defense. Recent studies implicate TLR polymorphisms in atherosclerosis risk in humans. Adipocyte fatty acid-binding protein (aP2) is present in macrophages and has an important role in atherosclerotic plaque development. We investigated aP2 expression in RAW 264.7 cells treated with lipopolysaccharide (LPS) and other TLR agonists and assessed lipid accumulation in these activated murine macrophages.


RESULTS
Stimulation with LPS, a TLR4 ligand, resulted in a 56-fold increase in aP2 mRNA expression, and zymosan, a TLR2 ligand, induced an approximately 1500-fold increase. Polyinosine: polycytidylic acid (poly I:C), a TLR3 ligand, led to a 9-fold increase. Levels of aP2 protein were significantly increased in LPS or zymosan-treated macrophages compared with control or poly I:C-treated cells. In addition, the cholesteryl ester content of LPS or zymosan-treated macrophages was approximately 5-fold greater in the presence of low-density lipoprotein, and triglyceride content was approximately 2-fold greater in the absence of exogenous lipid than control or poly I:C-treated cells.


CONCLUSIONS
Expression of macrophage aP2 is induced on TLR activation and parallels increases in cholesteryl ester and triglyceride levels. These results provide a molecular link between the known roles of TLR and aP2 in foam cell formation.
Kazemi
Mahmood R
MR
Metabolism Section, Department of Veterans Affairs Medical Center, San Francisco, Calif, CA 94121, USA. mkazemi@medicine.ucsf.edu
McDonald
Carol M
CM
Shigenaga
Judy K
JK
Grunfeld
Carl
C
Feingold
Kenneth R
KR
D000818:Animals; D050197:Atherosclerosis / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002788:Cholesterol Esters / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005487:Foam Cells / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D051193:Toll-Like Receptors / Q000819:agonists* / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*
D002788:Cholesterol Esters; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D014280:Triglycerides