Saquinavir-NO Inhibits IL-6 Production in Macrophages

被引:3
|
作者
Momcilovic, Miljana [1 ]
Mangano, Katia [2 ]
Jevtic, Bojan [1 ]
Mammana, Santa [2 ]
Stosic-Grujicic, Stanislava [1 ]
Nicoletti, Ferdinando [2 ,3 ]
Miljkovic, Djordje [1 ]
机构
[1] Univ Belgrade, Inst Biol Res Sinisa Stankovic, Dept Immunol, Belgrade, Serbia
[2] Univ Catania, Dept Biomed Sci, Catania, Italy
[3] OncoNOx Aps, Copenhagen, Denmark
关键词
TUMOR-ASSOCIATED MACROPHAGES; IN-VITRO; CANCER; DRUGS; INTERLEUKIN-6; INFLAMMATION; PROGRESSION; GENERATION; IMMUNITY;
D O I
10.1111/bcpt.12268
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Covalent attachment of the nitric oxide (NO) moiety to the HIV protease inhibitor Saquinavir (Saq) produced a new chemical entity, named Saquinavir-NO, (Saq-NO) with reduced toxicity and potent immunoregulatory influence on T lymphocytes. In this study, we have compared head-to-head the effects of Saq-NO and Saq on mouse and rat peritoneal macrophage cytokine secretion and NO production upon in vitro, ex vivo and in vivo conditions. The results demonstrate that Saq-NO, but not Saq, potently decreased interleukin (IL)-10, IL-6 and nitrite accumulation and increased the levels of IL-1 and tumour necrosis factor (TNF) in supernatants of mouse and rat macrophage cultures in vitro. Treatment of mice with Saq-NO, but not Saq, inhibited ex vivo secretion of IL-6 from macrophages. Consistent with these findings, Saq-NO also reduced blood levels of IL-6 in lipopolysaccharide-treated mice. The observed inhibitory influence of Saq-NO on IL-6 generation in macrophages may be involved in the observed antitumour and immunomodulatory effects of the drug.
引用
收藏
页码:499 / 506
页数:8
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