Expression of phosphatidylserine-specific phospholipase A(1) mRNA in human THP-1-derived macrophages

• Published in: Cell transplantation 2010, Vol.19 (6), p.759-764
• Main Authors: Hosono, Hiroyuki, Homma, Masato, Ogasawara, Yoko, Makide, Kumiko, Aoki, Junken, Niwata, Hideaki, Watanabe, Machiko, Inoue, Keizo, Ohkohchi, Nobuhiro, Kohda, Yukinao
• Format: Article
• Language: English
• Subjects: Adrenal Cortex Hormones - pharmacology; Cell Line; Dose-Response Relationship, Drug; Gene Expression Regulation, Enzymologic - drug effects; Humans; Immunosuppressive Agents - pharmacology; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Macrophages - enzymology; Phospholipases A1 - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Time Factors; Up-Regulation - drug effects
• ISSN: 0963-6897; 1555-3892
• DOI: 10.3727/096368910X508861

The expression of phosphatidylserine-specific phospholipase A(1) (PS-PLA(1)) 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-PLA(1) in peripheral blood cells responsible for the immune response may indicate a possible biological marker for rejection episodes. In this study, PS-PLA(1) 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-PLA(1) 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-PLA(1) mRNA. The time course of the mRNA expression profiles was different between PS-PLA(1) 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-PLA(1) 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-PLA(1) 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.