p38 Mitogen-activated protein kinase and phosphatidylinositol 3-kinase activities have opposite effects on human neutrophil apoptosis.
(2002) In FASEB Journal 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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/107047
- author
- Alvarado-Kristensson, Maria LU ; Ares, Isabella LU ; Grethe, Simone LU ; Smith, David ; Zheng, Limin and Andersson, Tommy LU
- organization
- publishing date
- 2002
- 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 Journal
- volume
- 16
- issue
- 1
- pages
- 31 - 129
- publisher
- Wiley
- external identifiers
-
- scopus:0036356391
- ISSN
- 1530-6860
- 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
- 2016-04-04 11:08:12
- date last changed
- 2023-09-06 09:05:25
@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}},
issn = {{1530-6860}},
keywords = {{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 = {{Wiley}},
series = {{FASEB Journal}},
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}},
doi = {{10.1096/fj.01-0817fje}},
volume = {{16}},
year = {{2002}},
}