Expression of phosphatidylserine-specific phospholipase A1 mRNA in human THP-1-derived macrophages

Hiroyuki Hosono, Masato Homma, Yoko Ogasawara, Kumiko Makide, Junken Aoki, Hideaki Niwata, Machiko Watanabe, Keizo Inoue, Nobuhiro Ohkohchi, Yukinao Kohda

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4 Citations (Scopus)

Abstract

The expression of phosphatidylserine-specific phospholipase A1 (PS-PLA1) is most upregulated in the genes of peripheral blood cells from chronic rejection model rats bearing long-term surviving cardiac allografts. The expression profile of PS-PLA1 in peripheral blood cells responsible for the immune response may indicate a possible biological marker for rejection episodes. In this study, PS-PLA1 mRNA expression was examined in human THP-1-derived macrophages. The effects of several immunosuppressive agents on this expression were also examined in in vitro experiments. A real-time RT-PCR analysis revealed that PS-PLA1 mRNA expression was found in human THP-1-derived macrophages. This expression was enhanced in the cells stimulated with lipopolysaccharide (LPS), a toll-like receptor (TLR) 4 ligand. Other TLR ligands (TLR2, 3, 5, 7, and 9) did not show a significant induction of PS-PLA1 mRNA. The time course of the mRNA expression profiles was different between PS-PLA1 and tumor necrosis factor-α (TNF-α), which showed a maximal expression at 12 and 1 h after LPS stimulation, respectively. Among the observed immunosuppressive agents, corticosteroids, prednisolone, 6α-methylprednisolone, dexamethasone, and beclomethasone inhibited PS-PLA1 expression with half-maximal inhibitory concentrations less than 3.0 nM, while methotrexate, cyclosporine A, tacrolimus, 6-mercaptopurine, and mycophenoic acid showed either a weak or moderate inhibition. These results suggest that the expression of PS-PLA1 mRNA in THP-1-derived macrophages is activated via TLR4 and it is inhibited by corticosteroids, which are used at high dosages to suppress chronic allograft rejection.

Original languageEnglish
Pages (from-to)759-764
Number of pages6
JournalCell Transplantation
Volume19
Issue number6-7
DOIs
Publication statusPublished - 2010

Keywords

  • Chronic rejection
  • Corticosteroids
  • Phosphatidylserine-specific phospholipase A (PS-PLA )
  • THP-1-derived macrophages
  • mRNA expression

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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    Hosono, H., Homma, M., Ogasawara, Y., Makide, K., Aoki, J., Niwata, H., Watanabe, M., Inoue, K., Ohkohchi, N., & Kohda, Y. (2010). Expression of phosphatidylserine-specific phospholipase A1 mRNA in human THP-1-derived macrophages. Cell Transplantation, 19(6-7), 759-764. https://doi.org/10.3727/096368910X508861