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- Publisher Website: 10.1084/jem.183.4.1447
- Scopus: eid_2-s2.0-0029880442
- PMID: 8666903
- WOS: WOS:A1996UH14400019
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Article: The role of interleukin 12 and nitric oxide in the development of spontaneous autoimmune disease in MRL/MP-lpr/lpr mice
Title | The role of interleukin 12 and nitric oxide in the development of spontaneous autoimmune disease in MRL/MP-lpr/lpr mice |
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Authors | |
Issue Date | 1996 |
Citation | Journal of Experimental Medicine, 1996, v. 183, n. 4, p. 1447-1459 How to Cite? |
Abstract | MRL/MP-lpr/lpr (MRL/lpr) mice develop a spontaneous autoimmune disease. Serum from these mice contained significantly higher concentrations of nitrite/nitrate than serum from age-matched control MRL/MP-+/+ (MRL/+), BALB/c or CBA/6J mice. Spleen and peritoneal cells from MRL/lpr mice also produced significantly more nitric oxide (NO) than those from the control mice when cultured with interferon (IFN) γ and lipopolysaccharide (LPS) in vitro. It is interesting to note that peritoneal cells from MRL/lpr mice also produced markedly higher concentrations of interleukin (IL) 12 than those from MRL/+ or BALB/c mice when cultured with the same stimuli. It is striking that cells from MRL/lpr mice produced high concentrations of NO witch cultured with IL-12 and IPS, whereas only low or background levels of NO were produced by similarly cultured cells from MRL/+ or BALB/c mice. The enhanced NO synthesis induced by IFN-γ/LPS was substantially inhibited by anti-IL-12 antibody. In addition, IL-12-induced NO production can also be markedly inhibited by anti-IFN-γ antibody, but only weakly inhibited by anti-tumor necrosis factor α antibody. The effect of IL-12 on NO production was dependent on the presence of natural killer and possibly T cells. Serum from MRL/lpr mice contained significantly higher concentrations of IL-12 compared with those of MRL/+ or BALB/c control mice. Daily injection of recombinant IL-12 led to increased serum levels of IFN-γ and NO metabolites, and accelerated glomerulonephritis in the young MRL/lpr mice (but not in the MRL/+ mice) compared with controls injected with phosphate-buffered saline alone. These data, together with previous finding that NO synthase inhibitors can ameliorate autoimmune disease in MRL/lpr mice, suggest that the high capacity of such mice to produce IL-12 and their greater responsiveness to IL-12, leading to the production of high concentrations of NO, are important factors in this spontaneous model of autoimmune disease. |
Persistent Identifier | http://hdl.handle.net/10722/200052 |
ISSN | 2023 Impact Factor: 12.6 2023 SCImago Journal Rankings: 6.838 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Huang, Fangping | - |
dc.contributor.author | Feng, Guijie | - |
dc.contributor.author | Lindop, George B M | - |
dc.contributor.author | Stott, David Ian | - |
dc.contributor.author | Liew, Fooyew | - |
dc.date.accessioned | 2014-07-26T23:11:04Z | - |
dc.date.available | 2014-07-26T23:11:04Z | - |
dc.date.issued | 1996 | - |
dc.identifier.citation | Journal of Experimental Medicine, 1996, v. 183, n. 4, p. 1447-1459 | - |
dc.identifier.issn | 0022-1007 | - |
dc.identifier.uri | http://hdl.handle.net/10722/200052 | - |
dc.description.abstract | MRL/MP-lpr/lpr (MRL/lpr) mice develop a spontaneous autoimmune disease. Serum from these mice contained significantly higher concentrations of nitrite/nitrate than serum from age-matched control MRL/MP-+/+ (MRL/+), BALB/c or CBA/6J mice. Spleen and peritoneal cells from MRL/lpr mice also produced significantly more nitric oxide (NO) than those from the control mice when cultured with interferon (IFN) γ and lipopolysaccharide (LPS) in vitro. It is interesting to note that peritoneal cells from MRL/lpr mice also produced markedly higher concentrations of interleukin (IL) 12 than those from MRL/+ or BALB/c mice when cultured with the same stimuli. It is striking that cells from MRL/lpr mice produced high concentrations of NO witch cultured with IL-12 and IPS, whereas only low or background levels of NO were produced by similarly cultured cells from MRL/+ or BALB/c mice. The enhanced NO synthesis induced by IFN-γ/LPS was substantially inhibited by anti-IL-12 antibody. In addition, IL-12-induced NO production can also be markedly inhibited by anti-IFN-γ antibody, but only weakly inhibited by anti-tumor necrosis factor α antibody. The effect of IL-12 on NO production was dependent on the presence of natural killer and possibly T cells. Serum from MRL/lpr mice contained significantly higher concentrations of IL-12 compared with those of MRL/+ or BALB/c control mice. Daily injection of recombinant IL-12 led to increased serum levels of IFN-γ and NO metabolites, and accelerated glomerulonephritis in the young MRL/lpr mice (but not in the MRL/+ mice) compared with controls injected with phosphate-buffered saline alone. These data, together with previous finding that NO synthase inhibitors can ameliorate autoimmune disease in MRL/lpr mice, suggest that the high capacity of such mice to produce IL-12 and their greater responsiveness to IL-12, leading to the production of high concentrations of NO, are important factors in this spontaneous model of autoimmune disease. | - |
dc.language | eng | - |
dc.relation.ispartof | Journal of Experimental Medicine | - |
dc.title | The role of interleukin 12 and nitric oxide in the development of spontaneous autoimmune disease in MRL/MP-lpr/lpr mice | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1084/jem.183.4.1447 | - |
dc.identifier.pmid | 8666903 | - |
dc.identifier.scopus | eid_2-s2.0-0029880442 | - |
dc.identifier.volume | 183 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 1447 | - |
dc.identifier.epage | 1459 | - |
dc.identifier.isi | WOS:A1996UH14400019 | - |
dc.identifier.issnl | 0022-1007 | - |