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Immunology logoLink to Immunology
. 1994 Apr;81(4):605–610.

Prostaglandins inhibit lipoprotein lipase gene expression in macrophages.

J B Desanctis 1, L Varesio 1, D Radzioch 1
PMCID: PMC1422386  PMID: 8039811

Abstract

In the present investigation of the effects of prostaglandin E2 (PGE2) on lipoprotein lipase (LPL) gene expression in macrophages, we observed that treatment of macrophages with PGE2 increased the levels of adenosine 3',5'-cyclic monophosphate (cAMP), while the addition of exogenous 5-bromo-cAMP to macrophage cultures resulted in down-regulation of LPL expression. Using indomethacin (INDO), an inhibitor of cyclo-oxygenase and prostaglandins production, we determined that PGE2 acts as a feedback inhibitor of LPL expression. We found that inhibited secretion of LPL protein in lipopolysaccharide (LPS)-treated macrophages could be restored to control levels by the addition of INDO to the medium. In contrast, INDO did not reverse the inhibition of LPL mRNA induced by LPS. Overall, our results have demonstrated that PGE2 is a potent inhibitor of LPL gene expression and indicated that its action may play an important physiological role in the regulation of LPL gene expression during bacterial infections.

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Selected References

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  1. Akahane K., Cohen R. B., Bickel M., Pluznik D. H. IL-1 alpha induces granulocyte-macrophage colony-stimulating factor gene expression in murine B lymphocyte cell lines via mRNA stabilization. J Immunol. 1991 Jun 15;146(12):4190–4196. [PubMed] [Google Scholar]
  2. Brandwein S. R. Regulation of interleukin 1 production by mouse peritoneal macrophages. Effects of arachidonic acid metabolites, cyclic nucleotides, and interferons. J Biol Chem. 1986 Jul 5;261(19):8624–8632. [PubMed] [Google Scholar]
  3. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  4. Doolittle M. H., Ben-Zeev O., Elovson J., Martin D., Kirchgessner T. G. The response of lipoprotein lipase to feeding and fasting. Evidence for posttranslational regulation. J Biol Chem. 1990 Mar 15;265(8):4570–4577. [PubMed] [Google Scholar]
  5. Espinoza-Delgado I., Longo D. L., Gusella G. L., Varesio L. IL-2 enhances c-fms expression in human monocytes. J Immunol. 1990 Aug 15;145(4):1137–1143. [PubMed] [Google Scholar]
  6. Gardette J., Margelin D., Maziere J. C., Bertrand J., Picard J. Effect of dibutyryl cyclic AMP and theophylline on lipoprotein lipase secretion by human monocyte-derived macrophages. FEBS Lett. 1987 Dec 10;225(1-2):178–182. doi: 10.1016/0014-5793(87)81153-5. [DOI] [PubMed] [Google Scholar]
  7. Gorospe M., Kumar S., Baglioni C. Tumor necrosis factor increases stability of interleukin-1 mRNA by activating protein kinase C. J Biol Chem. 1993 Mar 25;268(9):6214–6220. [PubMed] [Google Scholar]
  8. Harel-Bellan A., Brini A. T., Farrar W. L. IFN-gamma inhibits c-myc gene expression by impairing the splicing process in a colony-stimulating factor dependent murine myeloid cell line. J Immunol. 1988 Aug 1;141(3):1012–1017. [PubMed] [Google Scholar]
  9. Humes J. L., Bonney R. J., Pelus L., Dahlgren M. E., Sadowski S. J., Kuehl F. A., Jr, Davies P. Macrophages synthesis and release prostaglandins in response to inflammatory stimuli. Nature. 1977 Sep 8;269(5624):149–151. doi: 10.1038/269149a0. [DOI] [PubMed] [Google Scholar]
  10. Kather H., Simon B. Biphasic effects of prostaglandin E2 on the human fat cell adenylate cyclase. J Clin Invest. 1979 Aug;64(2):609–612. doi: 10.1172/JCI109500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kawakami M., Cerami A. Studies of endotoxin-induced decrease in lipoprotein lipase activity. J Exp Med. 1981 Sep 1;154(3):631–639. doi: 10.1084/jem.154.3.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kawakami M., Murase T., Ogawa H., Ishibashi S., Mori N., Takaku F., Shibata S. Human recombinant TNF suppresses lipoprotein lipase activity and stimulates lipolysis in 3T3-L1 cells. J Biochem. 1987 Feb;101(2):331–338. doi: 10.1093/oxfordjournals.jbchem.a121917. [DOI] [PubMed] [Google Scholar]
  13. Khoo J. C., Mahoney E. M., Witztum J. L. Secretion of lipoprotein lipase by macrophages in culture. J Biol Chem. 1981 Jul 25;256(14):7105–7108. [PubMed] [Google Scholar]
  14. Kirchgessner T. G., Svenson K. L., Lusis A. J., Schotz M. C. The sequence of cDNA encoding lipoprotein lipase. A member of a lipase gene family. J Biol Chem. 1987 Jun 25;262(18):8463–8466. [PubMed] [Google Scholar]
  15. Kurland J. I., Bockman R. Prostaglandin E production by human blood monocytes and mouse peritoneal macrophages. J Exp Med. 1978 Mar 1;147(3):952–957. doi: 10.1084/jem.147.3.952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mahoney E. M., Khoo J. C., Steinberg D. Lipoprotein lipase secretion by human monocytes and rabbit alveolar macrophages in culture. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1639–1642. doi: 10.1073/pnas.79.5.1639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nilsson-Ehle P., Schotz M. C. A stable, radioactive substrate emulsion for assay of lipoprotein lipase. J Lipid Res. 1976 Sep;17(5):536–541. [PubMed] [Google Scholar]
  18. Radzioch D., Clayton M., Varesio L. Interferon-alpha, -beta, and -gamma augment the levels of rRNA precursors in peritoneal macrophages but not in macrophage cell lines and fibroblasts. J Immunol. 1987 Aug 1;139(3):805–812. [PubMed] [Google Scholar]
  19. Radzioch D., Varesio L. c-fos mRNA expression in macrophages is downregulated by interferon-gamma at the posttranscriptional level. Mol Cell Biol. 1991 May;11(5):2718–2722. doi: 10.1128/mcb.11.5.2718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Renier G., Skamene E., DeSanctis J. B., Radzioch D. High macrophage lipoprotein lipase expression and secretion are associated in inbred murine strains with susceptibility to atherosclerosis. Arterioscler Thromb. 1993 Feb;13(2):190–196. doi: 10.1161/01.atv.13.2.190. [DOI] [PubMed] [Google Scholar]
  21. Renz H., Gong J. H., Schmidt A., Nain M., Gemsa D. Release of tumor necrosis factor-alpha from macrophages. Enhancement and suppression are dose-dependently regulated by prostaglandin E2 and cyclic nucleotides. J Immunol. 1988 Oct 1;141(7):2388–2393. [PubMed] [Google Scholar]
  22. Semenkovich C. F., Wims M., Noe L., Etienne J., Chan L. Insulin regulation of lipoprotein lipase activity in 3T3-L1 adipocytes is mediated at posttranscriptional and posttranslational levels. J Biol Chem. 1989 May 25;264(15):9030–9038. [PubMed] [Google Scholar]
  23. Sopher O., Goldman R. Bacterial lipopolysaccharide suppresses the expression of lipoprotein lipase in murine macrophages: a process independent of tumor necrosis factor or interleukin 1. Immunol Lett. 1987 Jul;15(3):261–265. doi: 10.1016/0165-2478(87)90034-4. [DOI] [PubMed] [Google Scholar]
  24. Sung S. J., Walters J. A. Stimulation of interleukin-1 alpha and interleukin-1 beta production in human monocytes by protein phosphatase 1 and 2A inhibitors. J Biol Chem. 1993 Mar 15;268(8):5802–5809. [PubMed] [Google Scholar]
  25. Tannenbaum C. S., Hamilton T. A. Lipopolysaccharide-induced gene expression in murine peritoneal macrophages is selectively suppressed by agents that elevate intracellular cAMP. J Immunol. 1989 Feb 15;142(4):1274–1280. [PubMed] [Google Scholar]
  26. Wang-Iverson P., Ungar A., Bliumis J., Bukberg P. R., Gibson J. C., Brown W. V. Human monocytes in culture synthesize and secrete lipoprotein lipase. Biochem Biophys Res Commun. 1982 Feb 11;104(3):923–928. doi: 10.1016/0006-291x(82)91337-7. [DOI] [PubMed] [Google Scholar]
  27. White J. R., Chait A., Klebanoff S. J., Deeb S., Brunzell J. D. Bacterial lipopolysaccharide reduces macrophage lipoprotein lipase levels: an effect that is independent of tumor necrosis factor. J Lipid Res. 1988 Oct;29(10):1379–1385. [PubMed] [Google Scholar]
  28. Wion K. L., Kirchgessner T. G., Lusis A. J., Schotz M. C., Lawn R. M. Human lipoprotein lipase complementary DNA sequence. Science. 1987 Mar 27;235(4796):1638–1641. doi: 10.1126/science.3823907. [DOI] [PubMed] [Google Scholar]

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