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Regulation of FAS Ligand Expression during Activation-Induced Cell Death in T Cells by p38 Mitogen-Activated Protein Kinase and C-Jun Nh(2)-Terminal Kinase

Activation-induced cell death (AICD) is a mechanism of peripheral T cell tolerance that depends upon an interaction between Fas and Fas ligand (FasL). Although c-Jun NH(2)-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) may be involved in apoptosis in various cell types, the mo...

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Autores principales: Zhang, Jian, Gao, Jian-Xin, Salojin, Kostantin, Shao, Qing, Grattan, Marsha, Meagher, Craig, Laird, Dale W., Delovitch, Terry L.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193110/
https://www.ncbi.nlm.nih.gov/pubmed/10727463
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author Zhang, Jian
Gao, Jian-Xin
Salojin, Kostantin
Shao, Qing
Grattan, Marsha
Meagher, Craig
Laird, Dale W.
Delovitch, Terry L.
author_facet Zhang, Jian
Gao, Jian-Xin
Salojin, Kostantin
Shao, Qing
Grattan, Marsha
Meagher, Craig
Laird, Dale W.
Delovitch, Terry L.
author_sort Zhang, Jian
collection PubMed
description Activation-induced cell death (AICD) is a mechanism of peripheral T cell tolerance that depends upon an interaction between Fas and Fas ligand (FasL). Although c-Jun NH(2)-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) may be involved in apoptosis in various cell types, the mode of regulation of FasL expression during AICD in T cells by these two MAPKs is incompletely understood. To investigate the regulatory roles of these two MAPKs, we analyzed the kinetics of TCR-induced p38 MAPK and JNK activity and their regulation of FasL expression and AICD. We report that both JNK and p38 MAPK regulate AICD in T cells. Our data suggest a novel model of T cell AICD in which p38 MAPK acts early to initiate FasL expression and the Fas-mediated activation of caspases. Subsequently, caspases stimulate JNK to further upregulate FasL expression. Thus, p38 MAPK and downstream JNK converge to regulate FasL expression at different times after T cell receptor stimulation to elicit maximum AICD.
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spelling pubmed-21931102008-04-16 Regulation of FAS Ligand Expression during Activation-Induced Cell Death in T Cells by p38 Mitogen-Activated Protein Kinase and C-Jun Nh(2)-Terminal Kinase Zhang, Jian Gao, Jian-Xin Salojin, Kostantin Shao, Qing Grattan, Marsha Meagher, Craig Laird, Dale W. Delovitch, Terry L. J Exp Med Original Article Activation-induced cell death (AICD) is a mechanism of peripheral T cell tolerance that depends upon an interaction between Fas and Fas ligand (FasL). Although c-Jun NH(2)-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) may be involved in apoptosis in various cell types, the mode of regulation of FasL expression during AICD in T cells by these two MAPKs is incompletely understood. To investigate the regulatory roles of these two MAPKs, we analyzed the kinetics of TCR-induced p38 MAPK and JNK activity and their regulation of FasL expression and AICD. We report that both JNK and p38 MAPK regulate AICD in T cells. Our data suggest a novel model of T cell AICD in which p38 MAPK acts early to initiate FasL expression and the Fas-mediated activation of caspases. Subsequently, caspases stimulate JNK to further upregulate FasL expression. Thus, p38 MAPK and downstream JNK converge to regulate FasL expression at different times after T cell receptor stimulation to elicit maximum AICD. The Rockefeller University Press 2000-03-20 /pmc/articles/PMC2193110/ /pubmed/10727463 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Zhang, Jian
Gao, Jian-Xin
Salojin, Kostantin
Shao, Qing
Grattan, Marsha
Meagher, Craig
Laird, Dale W.
Delovitch, Terry L.
Regulation of FAS Ligand Expression during Activation-Induced Cell Death in T Cells by p38 Mitogen-Activated Protein Kinase and C-Jun Nh(2)-Terminal Kinase
title Regulation of FAS Ligand Expression during Activation-Induced Cell Death in T Cells by p38 Mitogen-Activated Protein Kinase and C-Jun Nh(2)-Terminal Kinase
title_full Regulation of FAS Ligand Expression during Activation-Induced Cell Death in T Cells by p38 Mitogen-Activated Protein Kinase and C-Jun Nh(2)-Terminal Kinase
title_fullStr Regulation of FAS Ligand Expression during Activation-Induced Cell Death in T Cells by p38 Mitogen-Activated Protein Kinase and C-Jun Nh(2)-Terminal Kinase
title_full_unstemmed Regulation of FAS Ligand Expression during Activation-Induced Cell Death in T Cells by p38 Mitogen-Activated Protein Kinase and C-Jun Nh(2)-Terminal Kinase
title_short Regulation of FAS Ligand Expression during Activation-Induced Cell Death in T Cells by p38 Mitogen-Activated Protein Kinase and C-Jun Nh(2)-Terminal Kinase
title_sort regulation of fas ligand expression during activation-induced cell death in t cells by p38 mitogen-activated protein kinase and c-jun nh(2)-terminal kinase
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193110/
https://www.ncbi.nlm.nih.gov/pubmed/10727463
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