Abstract
We have studied the effects of dihydrocucurbitacin B, a triterpene isolated from Cayaponia tayuya roots, on different models of delayed type hypersensitivity (DTH) in mice, as well as on T-lymphocyte proliferation and the mediators involved. In experiments with mice, dihydrocucurbitacin B inhibited the inflammatory reactions induced by oxazolone, dinitrofluorobenzene, and sheep red blood cells, reducing both the edema and cell infiltration. Moreover, the analysis of inflamed tissues showed that dihydrocucurbitacin B reduced the presence of the most relevant cytokines implicated in these processes, including interleukin-1β, interleukin-4, and tumor necrosis factor-α. Dihydrocucurbitacin B was also found to inhibit the proliferation of phytohemagglutinin-stimulated human T lymphocytes (IC50 = 1.48 μM), halting the cell cycle in the G0 phase. In addition, the triterpene reduced the production of interleukin-2, interleukin-4, interleukin-10, and interferon-γ in human T lymphocytes, and it hampered the induction of the principal cyclins involved in the cell cycle, including A1, B1, D2, and E1. Finally, dihydrocucurbitacin B was found to exert a selective inhibition on the nuclear factor of activated T cells (NFAT) in human lymphocytes without affecting the calcium influx. Taken together, these results suggest that dihydrocucurbitacin B curbs DTH reactions by inhibiting NFAT, which in turn suppresses the proliferation of the most relevant cells involved in DTH reactions, namely the T cells.
Footnotes
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This work was supported by the Spanish Government (SAF2006-06726). J.M.E. is grateful for a fellowship from the Generalitat Valenciana, Grant CTBPRB/2003/315. We are also indebted to the Centre de Transfusions de la Comunitat Valenciana (Valencia, Spain) for its generous supply of human blood.
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doi:10.1124/jpet.107.122671.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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ABBREVIATIONS: TNF, tumor necrosis factor; DTH, delayed type hypersensitivity; SRBC, sheep red blood cell(s); Th, T helper; NFAT, nuclear factor of activated T cells; DHCB, dihydrocucurbitacin B; IL, interleukin; PHA, phytohemagglutinin; Tc, T cytotoxic.
- Received March 14, 2007.
- Accepted June 8, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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