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PKC epsilon is involved in JNK activation that mediates LPS-induced TNF-alpha, which induces apoptosis in macrophages.

Authors :
Comalada M
Xaus J
Valledor AF
López-López C
Pennington DJ
Celada A
Source :
American journal of physiology. Cell physiology [Am J Physiol Cell Physiol] 2003 Nov; Vol. 285 (5), pp. C1235-45. Date of Electronic Publication: 2003 Jul 16.
Publication Year :
2003

Abstract

Lipopolysaccharide (LPS) is a powerful stimulator of macrophages and induces apoptosis in these cells. Using primary cultures of bone marrow-derived macrophages, we found that the autocrine production of tumor necrosis factor-alpha (TNF-alpha) has a major function in LPS-induced apoptosis. LPS activates PKC and regulates the different mitogen-activated protein kinases (MAPK). We aimed to determine its involvement either in the secretion of TNF-alpha or in the induction of apoptosis. Using specific inhibitors and mice with the gene for PKCepsilon disrupted, we found that LPS-induced TNF-alpha-dependent apoptosis is mostly mediated by PKCepsilon, which is not directly involved in the signaling mechanism of apoptosis but rather in the process of TNF-alpha secretion. In our cell model, all three MAPKs were involved in the regulation of TNF-alpha secretion, but at different levels. JNK mainly regulates TNF-alpha transcription and apoptosis, whereas ERK and p38 contribute to the regulation of TNF-alpha production, probably through posttranscriptional mechanisms. Only JNK activity is mediated by PKCepsilon in response to LPS and so plays a major role in TNF-alpha secretion and LPS-induced apoptosis. We demonstrated in macrophages that LPS involving PKCepsilon regulates JNK activity and produces TNF-alpha, which induces apoptosis.

Details

Language :
English
ISSN :
0363-6143
Volume :
285
Issue :
5
Database :
MEDLINE
Journal :
American journal of physiology. Cell physiology
Publication Type :
Academic Journal
Accession number :
12867362
Full Text :
https://doi.org/10.1152/ajpcell.00228.2003