Nitric oxide-mediated inhibition of caspase-dependent T lymphocyte proliferation

Raja S. Mahidhara*, Rosemary A. Hoffman, Sulan Huang, Amanda Wolf-Johnston, Yoram Vodovotz, Richard L. Simmons, Timothy R. Billiar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Nitric oxide (NO), a pleiotropic signaling molecule produced at sites of inflammation, is a powerful inhibitor of lymphocyte proliferation. Caspases, central effector proteases in apoptosis, have recently been implicated as critical mediators of T cell activation. We and others have shown that NO can inhibit caspases by S-nitrosylation, which is reversible by the reducing agent dithiothreitol (DTT). The purpose of the present study was to determine whether NO inhibits lymphocyte proliferation by modulating caspase activity. Caspase inhibition with z-VAD-fmk blocked T cell proliferation. NO-dependent inhibition of T cell proliferation was associated with an inhibition of caspase activity and activation, and this effect was reversible by DTT. Previous studies demonstrated inhibition of apoptosis through S-nitrosylation of caspases; the present studies extend this effect to inhibition of caspase-dependent T cell proliferation.

Original languageEnglish
Pages (from-to)403-411
Number of pages9
JournalJournal of Leukocyte Biology
Issue number3
StatePublished - Sep 2003
Externally publishedYes


  • Apoptosis
  • Cellular proliferation
  • S-nitrosylation
  • T cell


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