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HIV‐1 Tat protein concomitantly down‐regulates apical caspase‐10 and up‐regulates c‐FLIP in lymphoid T cells: A potential molecular mechanism to escape TRAIL cytotoxicity
Author(s) -
Gibellini Davide,
Carla Re Maria,
Ponti Cristina,
Vitone Francesca,
Bon Isabella,
Fabbri Greta,
Grazia Di Iasio Maria,
Zauli Giorgio
Publication year - 2005
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20252
Subject(s) - jurkat cells , transfection , microbiology and biotechnology , biology , apoptosis , messenger rna , cell culture , complementary dna , gene , t cell , immunology , biochemistry , immune system , genetics
Abstract In this study, we showed the existence of a positive correlation between the amount of human immunodeficiency virus‐type 1 (HIV‐1) RNA in HIV‐1 seropositive subjects and the plasma levels of TRAIL. Since it has been previously demonstrated that HIV‐1 Tat protein up‐regulates the expression of TRAIL in monocytic cells whereas tat ‐expressing lymphoid cells are more resistant to TRAIL cytotoxicity, we next investigated the effect of Tat on the expression/activity of both apical caspase‐8 and ‐10, which play a key role in mediating the initial phases of apoptosis by TRAIL, and c‐FLIP. Jurkat lymphoblastoid human T cell lines stably transfected with a plasmid expressing wild‐type (HIV‐1) tat gene showed normal levels of caspase‐8 but significantly decreased levels of caspase‐10 at both mRNA and protein levels with respect to Jurkat transfected with the control plasmid or with a mutated (cys22) non‐functional tat cDNA. A significant decrease of caspase‐10 expression/activity was also observed in transient transfection experiments with plasmid carrying tat cDNA. Moreover, c‐FLIP L and c‐FLIP S isoforms were up‐regulated in tat ‐expressing cells at both mRNA and protein level in comparison with control cells. Taken together, these results provide a molecular basis to explain the resistance of tat ‐expressing Jurkat cells to apoptosis induced by TRAIL and, possibly, to other death‐inducing ligands. © 2004 Wiley‐Liss, Inc.