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p38 Mitogen-activated protein kinase and phosphatidylinositol 3-kinase activities have opposite effects on human neutrophil apoptosis.

Alvarado-Kristensson, Maria LU ; Ares, Isabella LU ; Grethe, Simone LU ; Smith, David; Zheng, Limin and Andersson, Tommy LU (2002) In FASEB J 16(1). p.31-129
Abstract
Neutrophil apoptosis is essential for resolution of inflammatory reactions. Here, we studied the role of two apoptosis/survival-associated protein kinases in this process. We discovered a previously undetected early and transient inhibition of the activity of p38 mitogen-activated protein kinase (p38 MAPK) during both spontaneous and Fas-induced apoptosis. Pharmacological inhibition of this enzyme augmented the activation of caspases and the apoptotic response, which suggests that the p38 MAPK signals survival in neutrophils. Our finding that caspase-3 activity was initiated during the transient inhibition of p38 MAPK suggests that apoptosis is initiated during this inhibition. Furthermore, such transient inhibition was counteracted by... (More)
Neutrophil apoptosis is essential for resolution of inflammatory reactions. Here, we studied the role of two apoptosis/survival-associated protein kinases in this process. We discovered a previously undetected early and transient inhibition of the activity of p38 mitogen-activated protein kinase (p38 MAPK) during both spontaneous and Fas-induced apoptosis. Pharmacological inhibition of this enzyme augmented the activation of caspases and the apoptotic response, which suggests that the p38 MAPK signals survival in neutrophils. Our finding that caspase-3 activity was initiated during the transient inhibition of p38 MAPK suggests that apoptosis is initiated during this inhibition. Furthermore, such transient inhibition was counteracted by granulocyte-macrophage colony-stimulating factor, which elicits survival. We also found that neither this inhibition of p38 MAPK nor the spontaneous apoptotic response depended on Fas. Instead, the early inhibition of p38 MAPK concurred with a Fas-induced activation of phosphatidylinositol 3-kinase, inhibition of which reduced apoptosis. Thus, the Fas-induced augmentation of spontaneous apoptosis can be explained by its activation of phosphatidylinositol 3-kinase. We conclude that p38 MAPK activity represents a survival signal that is inactivated transiently during both spontaneous and Fas-induced apoptosis, whereas Fas-induced phosphatidylinositol 3-kinase activity is a proapoptotic signal in isolated human neutrophils. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cysteine Proteinase Inhibitors, Human, Mitogen-Activated Protein Kinases, Oligopeptides, Imidazoles, Pharmacology, Cell Survival, 1-Phosphatidylinositol 3-Kinase
in
FASEB J
volume
16
issue
1
pages
31 - 129
publisher
The Federation of American Societies for Experimental Biology
external identifiers
  • scopus:0036356391
DOI
10.1096/fj.01-0817fje
language
English
LU publication?
yes
id
fa2d8782-3a00-4dd0-9698-52e939a349a2 (old id 107047)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11729103&dopt=Abstract
date added to LUP
2007-07-24 10:33:15
date last changed
2017-01-29 04:23:09
@article{fa2d8782-3a00-4dd0-9698-52e939a349a2,
  abstract     = {Neutrophil apoptosis is essential for resolution of inflammatory reactions. Here, we studied the role of two apoptosis/survival-associated protein kinases in this process. We discovered a previously undetected early and transient inhibition of the activity of p38 mitogen-activated protein kinase (p38 MAPK) during both spontaneous and Fas-induced apoptosis. Pharmacological inhibition of this enzyme augmented the activation of caspases and the apoptotic response, which suggests that the p38 MAPK signals survival in neutrophils. Our finding that caspase-3 activity was initiated during the transient inhibition of p38 MAPK suggests that apoptosis is initiated during this inhibition. Furthermore, such transient inhibition was counteracted by granulocyte-macrophage colony-stimulating factor, which elicits survival. We also found that neither this inhibition of p38 MAPK nor the spontaneous apoptotic response depended on Fas. Instead, the early inhibition of p38 MAPK concurred with a Fas-induced activation of phosphatidylinositol 3-kinase, inhibition of which reduced apoptosis. Thus, the Fas-induced augmentation of spontaneous apoptosis can be explained by its activation of phosphatidylinositol 3-kinase. We conclude that p38 MAPK activity represents a survival signal that is inactivated transiently during both spontaneous and Fas-induced apoptosis, whereas Fas-induced phosphatidylinositol 3-kinase activity is a proapoptotic signal in isolated human neutrophils.},
  author       = {Alvarado-Kristensson, Maria and Ares, Isabella and Grethe, Simone and Smith, David and Zheng, Limin and Andersson, Tommy},
  keyword      = {Cysteine Proteinase Inhibitors,Human,Mitogen-Activated Protein Kinases,Oligopeptides,Imidazoles,Pharmacology,Cell Survival,1-Phosphatidylinositol 3-Kinase},
  language     = {eng},
  number       = {1},
  pages        = {31--129},
  publisher    = {The Federation of American Societies for Experimental Biology},
  series       = {FASEB J},
  title        = {p38 Mitogen-activated protein kinase and phosphatidylinositol 3-kinase activities have opposite effects on human neutrophil apoptosis.},
  url          = {http://dx.doi.org/10.1096/fj.01-0817fje},
  volume       = {16},
  year         = {2002},
}