Skip to main content
NCBI home page
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1996 Feb;5(1):14–17. doi: 10.1155/S0962935196000026

Modulation of macrophage activation by prostaglandins

L Sautebin 1,✉, R Carnuccio 1, F D'Acquisto 1, M Di Rosa 1
PMCID: PMC2365772  PMID: 18475691

Abstract

The effect of prostaglandtn E2, iloprost and cAMP on both nitric oxide and tumour necrosis factor-α release in J774 macrophages has been studied. Both prostaglandin E2 and iloprost inhibited, in a concentration-dependent fashion, the lipopolysaccharide-induced generation of nitric oxide and tumour necrosis factor-α. The inhibitory effect of these prostanoids seems to be mediated by an increase of the second messenger cAMP since it was mimicked by dibutyryl cAMP and potentiated by the selective type IV phosphodiesterase inhibitor RO-20-1724. Our results suggest that the inhibition of nitric oxide release by prostaglandin E2 and iloprost in lipopolysaccharide-activated J774 macrophages may be secondary to the inhibition of tumour necrosis factor-α generation, which in turn is likely to be mediated by cAMP.

Full Text

The Full Text of this article is available as a PDF (373.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bachwich P. R., Chensue S. W., Larrick J. W., Kunkel S. L. Tumor necrosis factor stimulates interleukin-1 and prostaglandin E2 production in resting macrophages. Biochem Biophys Res Commun. 1986 Apr 14;136(1):94–101. doi: 10.1016/0006-291x(86)90881-8. [DOI] [PubMed] [Google Scholar]
  2. Dayer J. M., Beutler B., Cerami A. Cachectin/tumor necrosis factor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts. J Exp Med. 1985 Dec 1;162(6):2163–2168. doi: 10.1084/jem.162.6.2163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Drapier J. C., Wietzerbin J., Hibbs J. B., Jr Interferon-gamma and tumor necrosis factor induce the L-arginine-dependent cytotoxic effector mechanism in murine macrophages. Eur J Immunol. 1988 Oct;18(10):1587–1592. doi: 10.1002/eji.1830181018. [DOI] [PubMed] [Google Scholar]
  4. Endres S., Fülle H. J., Sinha B., Stoll D., Dinarello C. A., Gerzer R., Weber P. C. Cyclic nucleotides differentially regulate the synthesis of tumour necrosis factor-alpha and interleukin-1 beta by human mononuclear cells. Immunology. 1991 Jan;72(1):56–60. [PMC free article] [PubMed] [Google Scholar]
  5. Estrada C., Gómez C., Martín C., Moncada S., González C. Nitric oxide mediates tumor necrosis factor-alpha cytotoxicity in endothelial cells. Biochem Biophys Res Commun. 1992 Jul 15;186(1):475–482. doi: 10.1016/s0006-291x(05)80832-0. [DOI] [PubMed] [Google Scholar]
  6. Green L. C., Wagner D. A., Glogowski J., Skipper P. L., Wishnok J. S., Tannenbaum S. R. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem. 1982 Oct;126(1):131–138. doi: 10.1016/0003-2697(82)90118-x. [DOI] [PubMed] [Google Scholar]
  7. Hibbs J. B., Jr, Taintor R. R., Vavrin Z., Rachlin E. M. Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun. 1988 Nov 30;157(1):87–94. doi: 10.1016/s0006-291x(88)80015-9. [DOI] [PubMed] [Google Scholar]
  8. Kawakami M., Ishibashi S., Ogawa H., Murase T., Takaku F., Shibata S. Cachectin/TNF as well as interleukin-1 induces prostacyclin synthesis in cultured vascular endothelial cells. Biochem Biophys Res Commun. 1986 Dec 15;141(2):482–487. doi: 10.1016/s0006-291x(86)80198-x. [DOI] [PubMed] [Google Scholar]
  9. Kunkel S. L., Spengler M., May M. A., Spengler R., Larrick J., Remick D. Prostaglandin E2 regulates macrophage-derived tumor necrosis factor gene expression. J Biol Chem. 1988 Apr 15;263(11):5380–5384. [PubMed] [Google Scholar]
  10. Masferrer J. L., Seibert K., Zweifel B., Needleman P. Endogenous glucocorticoids regulate an inducible cyclooxygenase enzyme. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3917–3921. doi: 10.1073/pnas.89.9.3917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Peters T., Karck U., Decker K. Interdependence of tumor necrosis factor, prostaglandin E2, and protein synthesis in lipopolysaccharide-exposed rat Kupffer cells. Eur J Biochem. 1990 Aug 17;191(3):583–589. doi: 10.1111/j.1432-1033.1990.tb19161.x. [DOI] [PubMed] [Google Scholar]
  12. Raddassi K., Petit J. F., Lemaire G. LPS-induced activation of primed murine peritoneal macrophages is modulated by prostaglandins and cyclic nucleotides. Cell Immunol. 1993 Jun;149(1):50–64. doi: 10.1006/cimm.1993.1135. [DOI] [PubMed] [Google Scholar]
  13. Reeves M. L., Leigh B. K., England P. J. The identification of a new cyclic nucleotide phosphodiesterase activity in human and guinea-pig cardiac ventricle. Implications for the mechanism of action of selective phosphodiesterase inhibitors. Biochem J. 1987 Jan 15;241(2):535–541. doi: 10.1042/bj2410535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES