J. Lipid Res.
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J. Lipid Res., doi:10.1194/jlr.M300342-JLR200
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Submitted on August 4, 2003
Revised on November 21, 2003
Accepted on January 21, 2004

Induction of lysosomal phospholipase A2 through the retinoid X receptor in THP-1 cells

Akira Abe, Heather K. Poucher, Miki Hiraoka, and James A. Shayman

Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0676

Corresponding Author: jshayman{at}umich.edu

A novel lysosomal phospholipase A2 (LPLA2) was recently purified and cloned from bovine brain. THP-1 cells were employed to characterize the gene induction of this lipase. THP-1 cells were stimulated with agonists that induce THP-1 cell differentiation. The mRNA levels and the activity of LPLA2 increased in phorbol ester treated cells. However, vitamin D3, interferon-gamma and GMCSF did not have any effect on either mRNA expression or activity of LPLA2. All-trans-retinoic acid (ATRA) enhanced the mRNA expression and the activity of LPLA2 in a dose and time dependent manner. The retinoic acid isomers, 9-cis and 13-cis retinoic acids, also had the same effect as ATRA. The nuclear receptors, 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 LPLA2 induction by retinoic acid. The RAR agonist, TTNPB, resulted in a minimal increase of the mRNA expression and activity of LPLA2. However, the RXR agonist, methoprene acid, worked as well as RA in increasing both mRNA and enzyme activity. PPAR-gamma agonists failed to induce LPLA2 activity and mRNA. Thus an RXR-dependent pathway controls LPLA2 gene activation by retinoic acid in THP-1 cells.


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