Specific inhibition by prostaglandin D2 and its metabolites of lysozyme synthesis in mouse macrophage-like cell line, Mm-1.
The cultured mouse macrophage-like cell line Mm-1 synthesizes and secretes lysozyme continuously like normal macrophages. Culture of the cells in the presence of prostaglandin D2 for 3 days strongly inhibited their production of lysozyme activity. Prostaglandin D2 caused dose-dependent inhibition of the activity: 1 X 10(-6) M prostaglandin D2 caused about 50% inhibition. Inhibition by prostaglandin D2 was not related to cytotoxicity and was reversible. The rate of synthesis of lysozyme protein was measured by culturing Mm-1 cells with radioactive amino acids and then immunoprecipitating the protein. At the concentrations used, prostaglandin D2 inhibited the synthesis of lysozyme dose-dependently, but did not suppress the synthesis of total protein. Of the various types of prostaglandin, only prostaglandin D2 inhibited the production of lysozyme in Mm-1 cells. Moreover, prostaglandin D2 did not inhibit the production of other lysosomal enzymes, such as acid proteinase, acid phosphatase and beta-glucuronidase, and did not affect Fc receptors on the cell surface, adherence of cells to the culture dish or the cell morphology. These results indicate that prostaglandin D2 specifically inhibits the synthesis of lysozyme in Mm-1 cells. When Mm-1 cells were cultured for 3 days in the presence of the ethyl acetate extract from the culture medium in which Mm-1 cells had been cultured with prostaglandin D2 for 3 days, the production of lysozyme activity of Mm-1 cells was also markedly inhibited by the extract. After the incubation of prostaglandin D2 for 3 days with Mm-1 cells, less than 10% of the initial prostaglandin D2 remained and two major metabolites appeared. These results suggest that the metabolites of prostaglandin D2 were involved in the inhibitory action of prostaglandin D2 in Mm-1 cells.
D000818:Animals; D002460:Cell Line; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute; D008247:Lysosomes / Q000201:enzymology; D008264:Macrophages / Q000201:enzymology*; D051379:Mice; D009113:Muramidase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000378:metabolism / Q000494:pharmacology*; D014176:Protein Biosynthesis
D011457:Prostaglandins D; D009113:Muramidase; D015230:Prostaglandin D2