TY - JOUR
T1 - Inhibition of the CD8+ T cell-mediated cytotoxicity reaction by hypericin
T2 - Potential for treatment of T cell-mediated diseases
AU - Lavie, Gad
AU - Meruelo, Daniel
AU - Aroyo, Karin
AU - Mandel, Mathilda
PY - 2000
Y1 - 2000
N2 - The cytotoxicity reaction of murine CD8 T lymphocytes has been found to be strongly inhibited by nanomolar concentrations of hypericin, a lipophilic dianthraquinone with photodynamic properties. Cytotoxic T lymphocyte (CTL)-induced target cell apoptosis, as well as exocytosis of cytolytic granules from these cells, were ablated by hypericin, administered at the onset of the reaction, without affecting CTL viability. The inhibition of cytolysis occurred without the light irradiation which is essential for photosensitization. The findings suggest that the action of hypericin targets the effector CTL; however, apoptosis induced in murine L-cells with recombinant tumor necrosis factor (TNF)-α was also prevented by hypericin. Since hypericin is a known inhibitor of protein kinase C, MAP kinase and at least one other tyrosine kinase, this inhibitory activity could play a role in the down-modulation of CTL-induced cytotoxicity. Furthermore, our studies show that the action of hypericin induces rapid dephosphorylation of phospholipids associated with low-density membranes in CTL, but not with membranes of the cytotoxic granules. The ability of hypericin to interfere with cytotoxicity may render it useful in the treatment of T cell-mediated diseases.
AB - The cytotoxicity reaction of murine CD8 T lymphocytes has been found to be strongly inhibited by nanomolar concentrations of hypericin, a lipophilic dianthraquinone with photodynamic properties. Cytotoxic T lymphocyte (CTL)-induced target cell apoptosis, as well as exocytosis of cytolytic granules from these cells, were ablated by hypericin, administered at the onset of the reaction, without affecting CTL viability. The inhibition of cytolysis occurred without the light irradiation which is essential for photosensitization. The findings suggest that the action of hypericin targets the effector CTL; however, apoptosis induced in murine L-cells with recombinant tumor necrosis factor (TNF)-α was also prevented by hypericin. Since hypericin is a known inhibitor of protein kinase C, MAP kinase and at least one other tyrosine kinase, this inhibitory activity could play a role in the down-modulation of CTL-induced cytotoxicity. Furthermore, our studies show that the action of hypericin induces rapid dephosphorylation of phospholipids associated with low-density membranes in CTL, but not with membranes of the cytotoxic granules. The ability of hypericin to interfere with cytotoxicity may render it useful in the treatment of T cell-mediated diseases.
KW - Apoptosis
KW - Cytotoxic T lymphocyte
KW - Cytotoxicity
KW - Hypericin
KW - Protein kinase C
KW - Tumor necrosis factor-α
UR - http://www.scopus.com/inward/record.url?scp=0034042262&partnerID=8YFLogxK
U2 - 10.1093/intimm/12.4.479
DO - 10.1093/intimm/12.4.479
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C2 - 10744649
AN - SCOPUS:0034042262
SN - 0953-8178
VL - 12
SP - 479
EP - 486
JO - International Immunology
JF - International Immunology
IS - 4
ER -