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. 1996 Feb;5(1):62–68. doi: 10.1155/S0962935196000117

Nitric oxide production in murine spleen cells: role of interferons and prostaglandin E2 in the generation of cytotoxic activity

Dominique Vaillier 1, Richard Daculsi 1,✉, Norbert Gualdel 1,2
PMCID: PMC2365773  PMID: 18475700

Abstract

The production of nitric oxide (NO) was measured in cultures of spleen cells stimulated by lipopolysaccharide (LPS), IL-2 or LPS + IL-2. We observed that NO synthesis is increased by IFN-γ but inhibited by IFN-α/β. This is not the case when IL-2 is present in the cultures, since interferons play a minor role in the regulation of the NO production. When IL-2 and LPS were associated in the cultures, the IFN-α/β role seems more important than that of IFN-γ. PGE2 inhibits NO production in LPS supplemented cultures but has a slight effect in the presence of IL-2 and no effect with IL-2 + LPS. 3-isoButyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterases, induces a decrease of IFN production. In the presence of H-7, an inhibitor of protein kinase C (PKC), NO production is reduced when the cultures are supplemented by LPS or IL-2 but not when IL-2 and LPS are both added. H-7 also reduced IFN production. In the presence of NG-monomethyl-L-arginine (N-MMA), an inhibitor of NO synthesis, IFN production was increased, with no change in the cytotoxic activity. Hence, interferons regulate NO production by mouse spleen cells and, in return, NO modulates the generation of IFN.

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Selected References

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  1. Betz M., Fox B. S. Prostaglandin E2 inhibits production of Th1 lymphokines but not of Th2 lymphokines. J Immunol. 1991 Jan 1;146(1):108–113. [PubMed] [Google Scholar]
  2. Bogdan C., Vodovotz Y., Paik J., Xie Q. W., Nathan C. Mechanism of suppression of nitric oxide synthase expression by interleukin-4 in primary mouse macrophages. J Leukoc Biol. 1994 Feb;55(2):227–233. doi: 10.1002/jlb.55.2.227. [DOI] [PubMed] [Google Scholar]
  3. Brüne B., Lapetina E. G. Phosphorylation of nitric oxide synthase by protein kinase A. Biochem Biophys Res Commun. 1991 Dec 16;181(2):921–926. doi: 10.1016/0006-291x(91)91279-l. [DOI] [PubMed] [Google Scholar]
  4. Bulut V., Severn A., Liew F. Y. Nitric oxide production by murine macrophages is inhibited by prolonged elevation of cyclic AMP. Biochem Biophys Res Commun. 1993 Sep 15;195(2):1134–1138. doi: 10.1006/bbrc.1993.2162. [DOI] [PubMed] [Google Scholar]
  5. Ding A., Nathan C. F., Graycar J., Derynck R., Stuehr D. J., Srimal S. Macrophage deactivating factor and transforming growth factors-beta 1 -beta 2 and -beta 3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-gamma. J Immunol. 1990 Aug 1;145(3):940–944. [PubMed] [Google Scholar]
  6. Farrar W. L., Anderson W. B. Interleukin-2 stimulates association of protein kinase C with plasma membrane. Nature. 1985 May 16;315(6016):233–235. doi: 10.1038/315233a0. [DOI] [PubMed] [Google Scholar]
  7. Friedrich B., Cantrell D. A., Gullberg M. Increased cyclic AMP levels block interleukin 2-induced protein kinase C substrate phosphorylation but not the mitogenic response. Eur J Immunol. 1989 Jun;19(6):1111–1116. doi: 10.1002/eji.1830190622. [DOI] [PubMed] [Google Scholar]
  8. Fujihara M., Connolly N., Ito N., Suzuki T. Properties of protein kinase C isoforms (beta II, epsilon, and zeta) in a macrophage cell line (J774) and their roles in LPS-induced nitric oxide production. J Immunol. 1994 Feb 15;152(4):1898–1906. [PubMed] [Google Scholar]
  9. Gessani S., Belardelli F., Pecorelli A., Puddu P., Baglioni C. Bacterial lipopolysaccharide and gamma interferon induce transcription of beta interferon mRNA and interferon secretion in murine macrophages. J Virol. 1989 Jun;63(6):2785–2789. doi: 10.1128/jvi.63.6.2785-2789.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hamilton T. A., Becton D. L., Somers S. D., Gray P. W., Adams D. O. Interferon-gamma modulates protein kinase C activity in murine peritoneal macrophages. J Biol Chem. 1985 Feb 10;260(3):1378–1381. [PubMed] [Google Scholar]
  11. Hamilton T. A., Gainey P. V., Adams D. O. Maleylated-BSA suppresses IFN-gamma-mediated Ia expression in murine peritoneal macrophages. J Immunol. 1987 Jun 15;138(12):4063–4068. [PubMed] [Google Scholar]
  12. Klimpel G. R., Infante A. J., Patterson J., Hess C. B., Asuncion M. Virus-induced interferon alpha/beta (IFN-alpha/beta) production by T cells and by Th1 and Th2 helper T cell clones: a study of the immunoregulatory actions of IFN-gamma versus IFN-alpha/beta on functions of different T cell populations. Cell Immunol. 1990 Jul;128(2):603–618. doi: 10.1016/0008-8749(90)90052-s. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Longley R. E., Stewart D., Roe K. G., Good R. A. Inhibition of murine lymphokine-activated killer (LAK) cell activity by adherent cells. Cell Immunol. 1989 Jul;121(2):225–236. doi: 10.1016/0008-8749(89)90021-x. [DOI] [PubMed] [Google Scholar]
  15. Newton R. C. Effect of interferon on the induction of human monocyte secretion of interleukin-1 activity. Immunology. 1985 Nov;56(3):441–449. [PMC free article] [PubMed] [Google Scholar]
  16. Riches D. W., Underwood G. A. Expression of interferon-beta during the triggering phase of macrophage cytocidal activation. Evidence for an autocrine/paracrine role in the regulation of this state. J Biol Chem. 1991 Dec 25;266(36):24785–24792. [PubMed] [Google Scholar]
  17. Salvemini D., Misko T. P., Masferrer J. L., Seibert K., Currie M. G., Needleman P. Nitric oxide activates cyclooxygenase enzymes. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7240–7244. doi: 10.1073/pnas.90.15.7240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Severn A., Wakelam M. J., Liew F. Y. The role of protein kinase C in the induction of nitric oxide synthesis by murine macrophages. Biochem Biophys Res Commun. 1992 Nov 16;188(3):997–1002. doi: 10.1016/0006-291x(92)91330-s. [DOI] [PubMed] [Google Scholar]
  19. Suk K., Somers S. D., Erickson K. L. Regulation of murine macrophage function by IL-4: IL-4 and IFN-gamma differentially regulate macrophage tumoricidal activation. Immunology. 1993 Dec;80(4):617–624. [PMC free article] [PubMed] [Google Scholar]
  20. Vaillier D., Daculsi R., Gualde N. Effects of lipopolysaccharide on interleukin-2-induced cytotoxic activity of murine splenocyte cultures: role of prostaglandin E2 and interferons. Cancer Immunol Immunother. 1992;35(6):395–400. doi: 10.1007/BF01789018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Vodovotz Y., Bogdan C., Paik J., Xie Q. W., Nathan C. Mechanisms of suppression of macrophage nitric oxide release by transforming growth factor beta. J Exp Med. 1993 Aug 1;178(2):605–613. doi: 10.1084/jem.178.2.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Weisz A., Oguchi S., Cicatiello L., Esumi H. Dual mechanism for the control of inducible-type NO synthase gene expression in macrophages during activation by interferon-gamma and bacterial lipopolysaccharide. Transcriptional and post-transcriptional regulation. J Biol Chem. 1994 Mar 18;269(11):8324–8333. [PubMed] [Google Scholar]

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