title: Induction of lysosomal phospholipase A2 through the retinoid X receptor in THP-1 cells.
abstract: An acidic phospholipase A(2) (LPLA(2)) was recently purified and cloned. THP-1 cells were used to characterize the gene induction of LPLA(2). THP-1 cells were stimulated with several differentiation agents. The LPLA(2) mRNA and activity increased in cells treated with phorbol ester but not with vitamin D3, interferon-gamma, or granulocyte macrophage colony-stimulating factor. All-trans-retinoic acid enhanced mRNA expression and enzyme activity in a dose- and time-dependent manner. The natural 9-cis and 13-cis isomers of retinoic acid enhanced transcription and activity. Two classes of nuclear receptors, the retinoic acid receptor (RAR) and the retinoid X receptor (RXR), mediate retinoic acid signaling. Specific RAR and RXR agonists were used to identify the nuclear receptor responsible for LPLA(2) induction by retinoic acid. Treatment with the RAR agonist 4-[E-2-tetrahydro-5,5,8,8-tetra-methyl-2-naphthalenyl]1-propenyl benzoic acid (TTNPB) resulted in a small and statistically significant increase of the mRNA expression and activity of LPLA(2). The RXR agonist methoprene acid worked as well as all-trans-retinoic acid at increasing both mRNA and enzyme activity. The methoprene acid and TTNPB effects were not synergistic. The peroxisome proliferator-activated receptor gamma agonists 15-deoxy-Delta(12,14)-prostaglandin J(2) and troglitazone failed to induce LPLA(2) activity and mRNA. Thus, an RXR-dependent pathway controls LPLA(2) gene activation by retinoic acid in THP-1 cells.
authors.affiliation: Nephrology Division, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Abe
authors.forename: Heather K
authors.initials: HK
authors.lastname: Poucher
authors.forename: Miki
authors.initials: M
authors.lastname: Hiraoka
authors.forename: James A
authors.initials: JA
authors.lastname: Shayman
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008247:Lysosomes / Q000201:enzymology* / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists; D010703:Phorbol Esters / Q000494:pharmacology; D010741:Phospholipases A / Q000235:genetics*; D054467:Phospholipases A2; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D018168:Receptors, Retinoic Acid / Q000819:agonists; D047488:Retinoid X Receptors / Q000819:agonists / Q000502:physiology*; D015533:Transcriptional Activation; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D047495:PPAR gamma; D010703:Phorbol Esters; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014212:Tretinoin; D010741:Phospholipases A; D054467:Phospholipases A2