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Inhibitory effect of the immunosuppressant FK506 on apoptotic cell death induced by HIV-1 gp120
Authors:Iwao Sekigawa  Kazuhiko Koshino  Takashi Hishikawa  Hiroshi Kaneko  Yoshinari Takasaki  Hiroshi Hashimoto  Shun-Ichi Hirose  Yoshio Inagaki  Naoki Yamamoto
Affiliation:(1) Division of Rheumatology, Department of Medicine, Juntendo University, School of Medicine, 2-1-1, Hongo, Bunkyo-ku, 113 Tokyo, Japan;(2) Department of Medicine, Izu-Nagaoka Hospital, Juntendo University, School of Medicine, 1129 Nagaoka-cho, Tagata-gun, 410-22 Shizuoka, Japan;(3) Department of Microbiology, Tokyo Medical and Dental University, School of Medicine, 1-5-45, Yushima, Bunkyo-ku, 113 Tokyo, Japan
Abstract:
Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 may play a central role in inducing immunoregulatory disorders after HIV infection. The apoptotic death of normal human peripheral blood mononuclear cells was induced by priming with gp120 followed by stimulation with an anti-T cell receptor (TCR) antibody. Tumor necrosis factor-agr produced by gp120-binding macrophages may be important to induce this cell death. Treatment of gp120-primed cells with an immunosuppressant (FK506) before TCR signaling inhibited apoptotic cell death, and this blocking effect of FK506 was concentration dependent. FK506 did not have any influence on cell growth and viability over the range of concentrations tested. These findings suggest that FK506 is a potentially useful drug in delaying the onset of AIDS after HIV infection.
Keywords:Human immunodeficiency virus type 1 (HIV-1)  gp120  apoptosis  tumor necrosis factor-  /content/x72448l1r7u426q7/xxlarge945.gif"   alt="  agr"   align="  BASELINE"   BORDER="  0"  >  FK506
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