title: Trafficking of endogenous smooth muscle cell cholesterol: a role for serum amyloid A and interleukin-1β.
abstract: OBJECTIVE
  Intracellular cholesterol distribution impacts cell function; however, processes influencing endogenous cholesterol trafficking remain largely unknown. Atherosclerosis is associated with vascular inflammation and these studies address the role of inflammatory mediators on smooth muscle cell cholesterol trafficking.
  
  
  RESULTS
  Interestingly, in the absence of an exogenous cholesterol source, serum amyloid A increased [(14)C] oleic acid incorporation into cholesteryl ester in rat smooth muscle cells, suggesting endogenous cholesterol trafficking to the endoplasmic reticulum. [(3)H] cholesteryl ester accumulated in cells prelabeled with [(3)H] cholesterol, confirming that serum amyloid A mediated the movement of endogenous cholesterol. Cholesterol movement was dependent upon functional endolysosomes. The cholesterol oxidase-sensitive pool of cholesterol decreased in serum amyloid A-treated cells. Furthermore, the mechanism whereby serum amyloid A induced cholesterol trafficking was determined to be via activation of expression of secretory phospholipase A(2), group IIA (sPLA(2)) and sPLA(2)-dependent activation of sphingomyelinase. Interestingly, although neither tumor necrosis factor-α nor interferon-γ induced cholesterol trafficking, interleukin-1β induced [(14)C] cholesteryl ester accumulation that was also dependent upon sPLA(2) and sphingomyelinase activities. Serum amyloid A activates smooth muscle cell interleukin-1β expression, and although the interleukin-1-receptor antagonist inhibited the interleukin-1β-induced cholesterol trafficking, it had no effect on the movement of cholesterol mediated by serum amyloid A.
  
  
  CONCLUSIONS
  These data support a role for inflammation in endogenous smooth muscle cell cholesterol trafficking from the plasma membrane to the endoplasmic reticulum.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, K207, 72 East Concord Street, Boston, MA 02118, USA.
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Pessolano
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Sullivan
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Seidl
authors.forename: Celeste B
authors.initials: CB
authors.lastname: Rich
authors.forename: Laura
authors.initials: L
authors.lastname: Liscum
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Stone
authors.forename: Jean D
authors.initials: JD
authors.lastname: Sipe
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Schreiber
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D002789:Cholesterol Oxidase / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism*; D053419:Lipoproteins, IDL / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D019301:Oleic Acid / Q000378:metabolism; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002788:Cholesterol Esters; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D053419:Lipoproteins, IDL; D017472:Receptors, Interleukin-1; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha; D019301:Oleic Acid; D007371:Interferon-gamma; D002784:Cholesterol; D002789:Cholesterol Oxidase; D054497:Phospholipases A2, Secretory; D013108:Sphingomyelin Phosphodiesterase