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Expression of membrane‐bound and soluble FasL in Fas‐ and FADD‐dependent T lymphocyte apoptosis induced by mildly oxidized LDL
Author(s) -
Alcouffe Julie,
Therville Nicole,
Ségui Bruno,
Nazzal Dani,
Blaes Nelly,
Salvayre Robert,
Thomsen Mogens,
Benoist Hervé
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0808fje
Subject(s) - fadd , fas ligand , jurkat cells , apoptosis , microbiology and biotechnology , fas receptor , chemistry , ceramide , caspase 8 , mapk/erk pathway , death domain , reactive oxygen species , signal transducing adaptor protein , signal transduction , biology , immune system , caspase 3 , caspase , t cell , immunology , biochemistry , programmed cell death
Apoptosis plays an essential role in atherosclerosis. Oxidized low‐density lipoproteins (oxLDL) and activated T lymphocytes are present in atherosclerotic lesions, and we have previously reported that oxLDL induce apoptosis of activated T lymphocytes. We now show that this is preceded by an increase of Fas and FasL expression. Fas and FasL overexpression was dependent on reactive oxygen species (ROS) production as well as ERK and JNK activation. In addition, oxLDL triggered an early production of soluble FasL by T lymphocytes. Blocking anti‐ Fas antibody or Fas‐Fc protein, but also antioxidant molecules and inhibitors of ERK and JNK, decreased oxLDL‐mediated apoptosis. Moreover, PHA‐activated murine lymphocytes lacking a functional Fas receptor were partially resistant to oxLDL. Finally, Jurkat T cells deficient for FADD, an adaptor protein required for Fas signaling, resisted oxLDL‐induced apoptosis. OxLDL triggered caspase 8 and 3 activation as well as ceramide production in PHA‐activated lymphocytes and in Jurkat cells. Caspase activation was completely impaired in FADD‐deficient cells, but ceramide production was not affected. Altogether, our results highlight the putative role of both membrane‐bound and soluble FasL in oxLDL‐induced Fas and FADD‐dependent apoptosis of T lymphocytes and suggest an involvement of ROS, ERK, and JNK in this process.