Dihydrocucurbitacin B inhibits delayed type hypersensitivity reactions by suppressing lymphocyte proliferation.
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-1 beta, interleukin-4, and tumor necrosis factor-alpha. Dihydrocucurbitacin B was also found to inhibit the proliferation of phytohemagglutinin-stimulated human T lymphocytes (IC(50) = 1.48 microM), halting the cell cycle in the G(0) phase. In addition, the triterpene reduced the production of interleukin-2, interleukin-4, interleukin-10, and interferon-gamma in human T lymphocytes, and it hampered the induction of the principal cyclins involved in the cell cycle, including A(1), B(1), D(2), and E(1). 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.
Escandell
José M
JM
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Spain.
Recio
M Carmen
MC
Máñez
Salvador
S
Giner
Rosa M
RM
Cerdá-Nicolás
Miguel
M
Gil-Benso
Rosario
R
Ríos
José-Luis
JL
D000818:Animals; D016213:Cyclins / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D004195:Disease Models, Animal; D006968:Hypersensitivity, Delayed / Q000188:drug therapy*; D007249:Inflammation / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors; D016192:Resting Phase, Cell Cycle; D014315:Triterpenes / Q000494:pharmacology*
D016213:Cyclins; D016207:Cytokines; D050778:NFATC Transcription Factors; D014315:Triterpenes; C523469:dihydrocucurbitacin B