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Exogenous nitric oxide regulates IFN-gamma plus lipopolysaccharide-induced nitric oxide synthase expression in mouse macrophages.
J Immunol 1995; 155(2):886-94JI

Abstract

This study was performed to determine the effects of nitric oxide (NO) on the expression of inducible NO synthase (iNOS) in mouse macrophages. We used the NO donor diethylamine dinitric oxide (DEA/NO) and the mouse macrophage cell line ANA-1 in these experiments. ANA-1 macrophages did not express iNOS mRNA either constitutively or following exposure to 100 U/ml IFN-gamma alone, to 10 ng/ml LPS alone, or to 200 microM DEA/NO alone. Similarly, ANA-1 macrophages did not express detectable levels of iNOS mRNA following treatment with 100 U/ml IFN-gamma plus 200 microM DEA/NO. However, IFN-gamma (100 U/ml) plus LPS (10 ng/ml) induced high levels of iNOS mRNA in ANA-1 macrophages after 6 h. Low concentrations of DEA/NO (approximately 1 to 12 microM) caused up to a 2.5-fold augmentation of IFN-gamma plus LPS-induced iNOS mRNA expression. In contrast, 200 microM DEA/NO suppressed IFN-gamma plus LPS-induced iNOS mRNA expression (60% decrease). The effects of DEA/NO were gene-specific because DEA/NO did not affect the IFN-gamma plus LPS-induced expression of TNF-alpha mRNA. Moreover, the biphasic effects of DEA/NO were specifically due to released NO. Diethylamine and nitrite were unable to regulate IFN-gamma plus LPS-induced gene expression in ANA-1 macrophages. Time-response experiments suggested that the effects of NO were short-lived and occurred early during the induction of iNOS gene expression. The effects of NO were not limited to iNOS mRNA expression but were apparent at the level of iNOS protein expression and enzymatic activity. Overall, these results suggest that NO has immunoregulatory effects and may control the extent and duration of cytokine- and/or endotoxin-induced iNOS expression in macrophages.

Authors+Show Affiliations

Macrophage Cell Biology Section, National Cancer Institute-Frederick Cancer Research and Development Center, National Institutes of Health, MD 21702, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

7541825

Citation

Sheffler, L A., et al. "Exogenous Nitric Oxide Regulates IFN-gamma Plus Lipopolysaccharide-induced Nitric Oxide Synthase Expression in Mouse Macrophages." Journal of Immunology (Baltimore, Md. : 1950), vol. 155, no. 2, 1995, pp. 886-94.
Sheffler LA, Wink DA, Melillo G, et al. Exogenous nitric oxide regulates IFN-gamma plus lipopolysaccharide-induced nitric oxide synthase expression in mouse macrophages. J Immunol. 1995;155(2):886-94.
Sheffler, L. A., Wink, D. A., Melillo, G., & Cox, G. W. (1995). Exogenous nitric oxide regulates IFN-gamma plus lipopolysaccharide-induced nitric oxide synthase expression in mouse macrophages. Journal of Immunology (Baltimore, Md. : 1950), 155(2), pp. 886-94.
Sheffler LA, et al. Exogenous Nitric Oxide Regulates IFN-gamma Plus Lipopolysaccharide-induced Nitric Oxide Synthase Expression in Mouse Macrophages. J Immunol. 1995 Jul 15;155(2):886-94. PubMed PMID: 7541825.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exogenous nitric oxide regulates IFN-gamma plus lipopolysaccharide-induced nitric oxide synthase expression in mouse macrophages. AU - Sheffler,L A, AU - Wink,D A, AU - Melillo,G, AU - Cox,G W, PY - 1995/7/15/pubmed PY - 1995/7/15/medline PY - 1995/7/15/entrez SP - 886 EP - 94 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 155 IS - 2 N2 - This study was performed to determine the effects of nitric oxide (NO) on the expression of inducible NO synthase (iNOS) in mouse macrophages. We used the NO donor diethylamine dinitric oxide (DEA/NO) and the mouse macrophage cell line ANA-1 in these experiments. ANA-1 macrophages did not express iNOS mRNA either constitutively or following exposure to 100 U/ml IFN-gamma alone, to 10 ng/ml LPS alone, or to 200 microM DEA/NO alone. Similarly, ANA-1 macrophages did not express detectable levels of iNOS mRNA following treatment with 100 U/ml IFN-gamma plus 200 microM DEA/NO. However, IFN-gamma (100 U/ml) plus LPS (10 ng/ml) induced high levels of iNOS mRNA in ANA-1 macrophages after 6 h. Low concentrations of DEA/NO (approximately 1 to 12 microM) caused up to a 2.5-fold augmentation of IFN-gamma plus LPS-induced iNOS mRNA expression. In contrast, 200 microM DEA/NO suppressed IFN-gamma plus LPS-induced iNOS mRNA expression (60% decrease). The effects of DEA/NO were gene-specific because DEA/NO did not affect the IFN-gamma plus LPS-induced expression of TNF-alpha mRNA. Moreover, the biphasic effects of DEA/NO were specifically due to released NO. Diethylamine and nitrite were unable to regulate IFN-gamma plus LPS-induced gene expression in ANA-1 macrophages. Time-response experiments suggested that the effects of NO were short-lived and occurred early during the induction of iNOS gene expression. The effects of NO were not limited to iNOS mRNA expression but were apparent at the level of iNOS protein expression and enzymatic activity. Overall, these results suggest that NO has immunoregulatory effects and may control the extent and duration of cytokine- and/or endotoxin-induced iNOS expression in macrophages. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/7541825/Exogenous_nitric_oxide_regulates_IFN_gamma_plus_lipopolysaccharide_induced_nitric_oxide_synthase_expression_in_mouse_macrophages_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=7541825 DB - PRIME DP - Unbound Medicine ER -