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
来源：
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY | 2014年 / 115卷 / 06期
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
相关论文
共 50 条
  • [41] Paroxetine differentially modulates LPS-induced TNFα and IL-6 production in mouse macrophages
    Durairaj, Haritha
    Steury, Michael D.
    Parameswaran, Narayanan
    [J]. INTERNATIONAL IMMUNOPHARMACOLOGY, 2015, 25 (02) : 485 - 492
  • [42] The in vivo and in vitro effects of an alkylating agent, mechlorethamine, on IL-6 production in mice and the role of macrophages
    Bryniarski, K
    Ptak, M
    Ptak, W
    [J]. IMMUNOPHARMACOLOGY, 1996, 34 (2-3): : 73 - 78
  • [43] IL-6 inhibits RANKL-induced osteoclastogenesis
    不详
    [J]. CALCIFIED TISSUE INTERNATIONAL, 2006, 78 : S77 - S77
  • [44] IL-6 MEDIATES AGE ASSOCIATED OVER-PRODUCTION OF IL-6 IN THE ADIPOSE TISSUE
    Starr, M. E.
    Evers, B. M.
    Saito, H.
    [J]. GERONTOLOGIST, 2009, 49 : 183 - 184
  • [45] GABA (A) receptor subunits RNA expression in mice peritoneal macrophages modulate their IL-6/IL-12 production
    Reyes-Garcia, Maria Guadalupe
    Hernandez-Hernandez, Francisca
    Hernandez-Tellez, Beatriz
    Garcia-Tamayo, Fernando
    [J]. JOURNAL OF NEUROIMMUNOLOGY, 2007, 188 (1-2) : 64 - 68
  • [46] Gram Positive Bacteria Induce IL-6 and IL-8 Production in Human Alveolar Macrophages and Epithelial Cells
    Britt-Marie Larsson
    Kjell Larsson
    Per Malmberg
    Lena Palmberg
    [J]. Inflammation, 1999, 23 (3) : 217 - 230
  • [47] HETEROGENEITY OF KUPFFER CELLS AND SPLENIC, ALVEOLAR, AND PERITONEAL-MACROPHAGES FOR THE PRODUCTION OF TNF, IL-1, AND IL-6
    OGLE, CK
    WU, JZ
    MA, XL
    SZCZUR, K
    ALEXANDER, JW
    OGLE, JD
    [J]. INFLAMMATION, 1994, 18 (05) : 511 - 523
  • [48] Gram positive bacteria induce IL-6 and IL-8 production in human alveolar macrophages and epithelial cells
    Larsson, BM
    Larsson, K
    Malmberg, P
    Palmberg, L
    [J]. INFLAMMATION, 1999, 23 (03) : 217 - 230
  • [49] Differential Regulation of IL-1β and IL-6 Release in Murine Macrophages
    Seishiro Hirano
    Quan Zhou
    Akiko Furuyama
    Sanae Kanno
    [J]. Inflammation, 2017, 40 : 1933 - 1943
  • [50] Dectin-1 interaction with tetraspanin CD37 inhibits IL-6 production
    Meyer-Wentrup, Friederike
    Figdor, Carl G.
    Ansems, Marleen
    Brossart, Peter
    Wright, Mark D.
    Adema, Gosse J.
    van Spriel, Annemiek B.
    [J]. JOURNAL OF IMMUNOLOGY, 2007, 178 (01): : 154 - 162
12345