NO-hybridization of the HIV protease inhibitor Saquinavir generates a new chemical entity named Saq-NO, that retains the anti-viral activity and exerts lower toxicity. We show that Saq-NO inhibited the generation of various cytokines in ConA-stimulated unfractionated murine spleen cells and rat lymph nodes stimulated with ConA as well as in purified CD4+ T cells in vitro and reduced the circulating levels of cytokines in mice challenged with anti-CD3 antibody. Furthermore, Saq-NO reduced IL-17 and IFN-γ production in myelin basic protein (MBP)-specific cells isolated from rats immunized with MBP. These findings translated well into the in vivo setting as Saq-NO ameliorated the course of the disease in two preclinical models of multiple sclerosis. Our results demonstrate that Saq-NO exerts immunomodulatory effects that warrant studies on its application in autoimmune diseases. © 2013 Elsevier B.V.
CITATION STYLE
Petković, F., Blaževski, J., Momčilović, M., Timotijević, G., Zocca, M. B., Mijatović, S., … Miljković, D. (2013). Saquinavir-NO inhibits S6 kinase activity, impairs secretion of the encephalytogenic cytokines interleukin-17 and interferon-gamma and ameliorates experimental autoimmune encephalomyelitis. Journal of Neuroimmunology, 259(1–2), 55–65. https://doi.org/10.1016/j.jneuroim.2013.03.010
Mendeley helps you to discover research relevant for your work.