Differential Role of p38 and c-Jun N-Terminal Kinase 1 Mitogen-Activated Protein Kinases in NK Cell Cytotoxicity

The serine-threonine mitogen-activated protein kinase (MAPK) family includes extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 kinases. In NK cells, spontaneous or Ab-mediated recognition of target cells leads to activation of an ERK-2 MAPK-dependent biochemical p...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 2000-08, Vol.165 (4), p.1782-1789
Main Authors: Trotta, Rossana, Fettucciari, Katia, Azzoni, Livio, Abebe, Bekele, Puorro, Kristin A, Eisenlohr, Laurence C, Perussia, Bice
Format: Article
Language:English
Subjects:
Actins - metabolism
Antibody-Dependent Cell Cytotoxicity - immunology
Cell Line
Cells, Cultured
Cytokines - biosynthesis
Cytokines - genetics
Cytokines - metabolism
Cytoplasmic Granules - immunology
Cytotoxicity Tests, Immunologic
Cytotoxicity, Immunologic - immunology
Enzyme Activation - immunology
ERK2 kinase
Exocytosis - immunology
Humans
JNK Mitogen-Activated Protein Kinases
JNK protein
K562 Cells
Killer Cells, Natural - enzymology
Killer Cells, Natural - immunology
Killer Cells, Natural - metabolism
Mitogen-Activated Protein Kinases - physiology
p38 Mitogen-Activated Protein Kinases
p38 protein
Receptors, IgG - physiology
RNA, Messenger - biosynthesis
RNA, Messenger - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The serine-threonine mitogen-activated protein kinase (MAPK) family includes extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 kinases. In NK cells, spontaneous or Ab-mediated recognition of target cells leads to activation of an ERK-2 MAPK-dependent biochemical pathway(s) involved in the regulation of NK cell effector functions. Here we assessed the roles of p38 and JNK MAPK in NK cell-mediated cytotoxicity. Our data indicate that p38 is activated in primary human NK cells upon stimulation with immune complexes and interaction with NK-sensitive target cells. FcgammaRIIIA-induced granule exocytosis and both spontaneous and Ab-dependent cytotoxicity were reduced in a dose-dependent manner in cells pretreated with either of two specific inhibitors of this kinase. Target cell-induced IFN-gamma and FcgammaRIIIA-induced TNF-alpha mRNA accumulation was similarly affected under the same conditions. Lack of inhibition of NK cell cytotoxicity in cells overexpressing an inactive form of JNK1 indicates that this kinase, activated only upon FcgammaRIIIA ligation, does not play a significant role in cytotoxicity. These data underscore the involvement of p38, but not JNK1, in the molecular mechanisms regulating NK cell cytotoxicity.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.165.4.1782