title: ADRP/ADFP and Mal1 expression are increased in macrophages treated with TLR agonists.
abstract: 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.
authors.affiliation: Metabolism Section, Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA. kenneth.feingold@ucsf.edu
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Feingold
authors.forename: Mahmood R
authors.initials: MR
authors.lastname: Kazemi
authors.forename: Amy L
authors.initials: AL
authors.lastname: Magra
authors.forename: Carol M
authors.initials: CM
authors.lastname: McDonald
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Chui
authors.forename: Judy K
authors.initials: JK
authors.lastname: Shigenaga
authors.forename: Sophie M
authors.initials: SM
authors.lastname: Patzek
authors.forename: Zoe W
authors.initials: ZW
authors.lastname: Chan
authors.forename: Constantine
authors.initials: C
authors.lastname: Londos
authors.forename: Carl
authors.initials: C
authors.lastname: Grunfeld
mesh_terms: 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
chemical_list: 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