Skip NavigationSkip to Content

Cyclosporin A blocks the expression of lymphotoxin alpha, but not lymphotoxin beta, in human peripheral blood mononuclear cells

  1. Author:
    Kuprash, D. V.
    Boitchenko, V. E.
    Yarovinsky, F. O.
    Rice, N. R.
    Nordheim, A.
    Ruhlmann, A.
    Nedospasov, S. A.
  2. Author Address

    Russian Acad Sci, Engelhardt Inst Mol Biol, Lab Mol Immunol, 32 Vavilov St, Moscow 119991, Russia Russian Acad Sci, Engelhardt Inst Mol Biol, Lab Mol Immunol, Moscow 119991, Russia Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow, Russia Univ Tubingen, Inst Cell Biol, Dept Mol Biol, Tubingen, Germany NCI, Div Basic Sci, Regulat Cell Growth Lab, Frederick, MD 21701 USA NCI, Div Basic Sci, Mol Immunoregulat Lab, Frederick, MD 21701 USA SAIC, Intramural Res Support Program, Frederick, MD USA Nedospasov SA Russian Acad Sci, Engelhardt Inst Mol Biol, Lab Mol Immunol, 32 Vavilov St, Moscow 119991, Russia
    1. Year: 2002
  1. Journal: Blood
    1. 100
    2. 5
    3. Pages: 1721-1727
  2. Type of Article: Article
  1. Abstract:

    The 2 lymphotoxin subunits LTalpha (also called tumor necrosis factor beta [TNF-beta]) and LTbeta belong to the family of TNF- related cytokines. They form either a soluble homotrimeric ligand (LTalpha(3)) that binds to and signals through CD120a/b (TNFRp55 and TNFRp75), or a membrane-associated heterotrimeric ligand (LTalpha(1)beta(2)) that binds to and signals through the LTbeta receptor (LTbetaR). In mice, LTbetaR signaling is critical for the maintenance of peripheral lymphoid tissues and optimal immune responses, and its down-regulation results in immunodeficiency. To determine the possible relationship between LT-mediated immunodeficiency and the immunosuppressive effects of cyclosporin A (CsA), we tested the effects of CsA on the expression of LTalpha and LTbeta in human peripheral blood mononuclear cells (PBMCs). When PBMCs were stimulated with phorbol myristate acetate/ionomycin or with anti- CD3/anti- CD28, the accumulation of LTalpha both at mRNA and protein levels was markedly inhibited by CsA. This inhibition is likely due to CsA's effect on the nuclear factor of activated T cell (NFAT) proteins binding to a novel NFAT-binding element at position -490 relative to LTalpha transcription start. LTbeta showed a distinct expression pattern and was insensitive to CsA. Thus, in addition to its effects on the expression of other TNF family members, such as TNFalpha, CD40-L, and CD95-L, CsA can block expression of surface LT complex by selectively inhibiting the expression of the LTalpha subunit. We propose that LT dysfunction and its downstream effects may contribute to immunosuppressive effects of CsA. (C) 2002 by The American Society of Hematology.

    See More

External Sources

  1. No sources found.

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel