ADRP/ADFP and Mal1 expression are increased in macrophages treated with TLR agonists.
Activation of macrophages by TLR agonists enhances foam cell formation, but the underlying mechanisms are not understood. We examined the effects of TLR agonists on ADRP/ADFP, a protein associated with forming lipid droplets, and Mal1 a fatty acid-binding protein, in two mouse macrophage cell lines and human monocytes. Low doses of LPS, a TLR4 agonist increased both mRNA and protein levels of ADRP/ADFP and Mal1 in RAW 264.7 macrophages. Following pretreatment with Intralipid, fatty acids, or acetyl-LDL to increase triglyceride or cholesterol ester storage, LPS treatment still increased ADRP/ADFP and Mal1 mRNA levels. LPS also induced ADRP/ADFP and Mal1 in J774 macrophages and ADRP/ADFP in human monocytes. Zymosan, a fungal product that activates TLR2, poly-I:C, a viral mimetic that activates TLR3, and imiquimod, a TLR7 agonist, also increased ADRP/ADFP. Zymosan, but not poly-I:C or imiquimod, induced Mal1. In contrast, neither gene was induced by TNFalpha, IL-1beta, IL-6, or interferon-gamma. Thus TLR agonists induce ADRP/ADFP and Mal1, which likely contributes to macrophage triglyceride and cholesterol ester storage leading to foam cell formation.
Feingold
Kenneth R
KR
Metabolism Section, Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA. kenneth.feingold@ucsf.edu
Kazemi
Mahmood R
MR
Magra
Amy L
AL
McDonald
Carol M
CM
Chui
Lisa G
LG
Shigenaga
Judy K
JK
Patzek
Sophie M
SM
Chan
Zoe W
ZW
Londos
Constantine
C
Grunfeld
Carl
C
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D050197:Atherosclerosis / Q000276:immunology*; D002788:Cholesterol Esters / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis*; D006801:Humans; D000077271:Imiquimod; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D000070780:Perilipin-2; D011070:Poly I-C / Q000494:pharmacology; D051193:Toll-Like Receptors / Q000819:agonists* / Q000276:immunology; D014280:Triglycerides / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
D000634:Aminoquinolines; D002788:Cholesterol Esters; C082667:Fabp5 protein, mouse; D050556:Fatty Acid-Binding Proteins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C000602982:PLIN2 protein, human; D000070780:Perilipin-2; C000602983:Plin2 protein, mouse; D051193:Toll-Like Receptors; D014280:Triglycerides; D015054:Zymosan; D011070:Poly I-C; D000077271:Imiquimod