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Nitric oxide‐mediated inhibition of caspase‐dependent T lymphocyte proliferation
Author(s) -
Mahidhara Raja S.,
Hoffman Rosemary A.,
Huang Sulan,
WolfJohnston Amanda,
Vodovotz Yoram,
Simmons Richard L.,
Billiar Timothy R.
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0602293
Subject(s) - caspase , biology , microbiology and biotechnology , apoptosis , nitric oxide , proteases , cell growth , effector , programmed cell death , caspase 3 , dithiothreitol , biochemistry , enzyme , endocrinology
Nitric oxide (NO), a pleiotropic signaling molecule produced at sites of inflammaion, 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.