Details

Autor(en) / Beteiligte

• Escandell, José M
• Recio, María-Carmen
• Giner, Rosa M
• Máñez, Salvador
• Cerdá-Nicolás, Miguel
• Merfort, Irmgard
• Ríos, José-Luis

Titel

Inhibition of delayed-type hypersensitivity by Cucurbitacin R through the curbing of lymphocyte proliferation and cytokine expression by means of nuclear factor AT translocation to the nucleus

Ist Teil von

• The Journal of pharmacology and experimental therapeutics, 2010-02, Vol.332 (2), p.352

Ort / Verlag

United States

Erscheinungsjahr

2010

Link zum Volltext

Beschreibungen/Notizen

• Cucurbitacin R is known to exhibit an anti-inflammatory effect in different experimental models of inflammation. In this article, we outline the effect of cucurbitacin R on T lymphocyte proliferation, cytokine production, and nuclear factor activation, as well as its influence on various experimental models of delayed-type hypersensitivity (DTH) in mice. Cucurbitacin R reduced the proliferation of phytohemagglutinin A-stimulated human T lymphocytes (IC(50), 18 microM), modifying the cell cycle, as well as the production of cytokines [interleukin (IL)-2, IL-4, IL-10, and especially interferon-gamma] and the induction of the principal cyclins implicated in the cell cycle (A(1), B(1), D(2), and E). These effects are brought on by a novel, selective inhibition of nuclear factor AT (NFAT) by cucurbitacin R, with no concomitant effect on other transcription factors such as activator protein-1. In addition, we tested the in vivo effects of cucurbitacin R in three experimental models of DTH, as well as its effects on T lymphocyte proliferation, the cell cycle, cytokines, and cyclins. Although cucurbitacin R was found to reduce the inflammatory response brought on by both oxazolone and dinitrofluorobenzene, its activity was even more pronounced against sheep red blood cell-induced edema in mouse paws, with a clear reduction in the production of IL-1beta, IL-4, and tumor necrosis factor alpha in the inflamed paw. In conclusion, cucurbitacin R has the potential to be a new immunosuppressive agent with antiproliferative effects through the inhibition of the NFAT with anti-inflammatory activity in DTH reactions.