Regulation of ferritin light chain gene expression by oxidized low-densitylipoproteins in human monocytic THP-1 cells

Genes induced or suppressed by oxidized low-density Lipoproteins (oxLDL) in human monocytic THP-1 cells were searched using differential display rever se transcriptase polymerase chain reactions (DDRT-PCR), Among the many diff erentially expressed cDNA fragments, one was dramatically stimulated by the oxLDL in a steady state level, which was later found to contain sequences corresponding to ferritin light chain (L-ferritin) in a sequence homology s earch. The stimulatory effect of the oxLDL on the level of L-ferritin mRNA in the THP-1 cells was both time- and dose-dependent. When the cells were a llowed to differentiate in the presence of phorbol la-myristate 13-acetate (PMA), the differentiated cells were generally less responsive to the oxLDL than the undifferentiated ones. An increase of L-ferritin mRNA was observe d when the cells were treated with the lipid components in the oxLDL such a s 9-HODE, 13-HODE, and 25-hydroxycholesterol. In addition, a stimulation of the L-ferritin gene expression was also observed when the cells were treat ed with an endogenous peroxisome proliferator-activated receptor gamma (PPA R gamma) ligand, 15d-PGJ2, in a time- and dose-dependent manner, These resu lts suggest that oxLDL or its constituents are related to the stimulation o f L-ferritin expression via PPAR gamma. (C) 1999 Academic Press.