MAPK-activated protein kinase 2-deficiency causes hyperacute tumor necrosis factor-induced inflammatory shock
- Author
- Benjamin Vandendriessche (UGent) , An Goethals, Alba Simats, Evelien Van Hamme (UGent) , Peter Brouckaert (UGent) and Anje Cauwels (UGent)
- Organization
- Abstract
- Background: MAPK-activated protein kinase 2 (MK2) plays a pivotal role in the cell response to (inflammatory) stress. Among others, MK2 is known to be involved in the regulation of cytokine mRNA metabolism and regulation of actin cytoskeleton dynamics. Previously, MK2-deficient mice were shown to be highly resistant to LPS/D-Galactosamine-induced hepatitis. Additionally, research in various disease models has indicated the kinase as an interesting inhibitory drug target for various acute or chronic inflammatory diseases. Results: We show that in striking contrast to the known resistance of MK2-deficient mice to a challenge with LPS/D-Gal, a low dose of tumor necrosis factor (TNF) causes hyperacute mortality via an oxidative stress driven mechanism. We identified in vivo defects in the stress fiber response in endothelial cells, which could have resulted in reduced resistance of the endothelial barrier to deal with exposure to oxidative stress. In addition, MK2-deficient mice were found to be more sensitive to cecal ligation and puncture-induced sepsis. Conclusions: The capacity of the endothelial barrier to deal with inflammatory and oxidative stress is imperative to allow a regulated immune response and maintain endothelial barrier integrity. Our results indicate that, considering the central role of TNF in pro-inflammatory signaling, therapeutic strategies examining pharmacological inhibition of MK2 should take potentially dangerous side effects at the level of endothelial barrier integrity into account.
- Keywords
- Inflammatory shock, MK2, Tumor necrosis factor, Reactive oxygen species, Actin cytoskeleton, Endothelial permeability, Cecal ligation and puncture
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-6849087
- MLA
- Vandendriessche, Benjamin, et al. “MAPK-Activated Protein Kinase 2-Deficiency Causes Hyperacute Tumor Necrosis Factor-Induced Inflammatory Shock.” BMC PHYSIOLOGY, vol. 14, 2014, doi:10.1186/s12899-014-0005-1.
- APA
- Vandendriessche, B., Goethals, A., Simats, A., Van Hamme, E., Brouckaert, P., & Cauwels, A. (2014). MAPK-activated protein kinase 2-deficiency causes hyperacute tumor necrosis factor-induced inflammatory shock. BMC PHYSIOLOGY, 14. https://doi.org/10.1186/s12899-014-0005-1
- Chicago author-date
- Vandendriessche, Benjamin, An Goethals, Alba Simats, Evelien Van Hamme, Peter Brouckaert, and Anje Cauwels. 2014. “MAPK-Activated Protein Kinase 2-Deficiency Causes Hyperacute Tumor Necrosis Factor-Induced Inflammatory Shock.” BMC PHYSIOLOGY 14. https://doi.org/10.1186/s12899-014-0005-1.
- Chicago author-date (all authors)
- Vandendriessche, Benjamin, An Goethals, Alba Simats, Evelien Van Hamme, Peter Brouckaert, and Anje Cauwels. 2014. “MAPK-Activated Protein Kinase 2-Deficiency Causes Hyperacute Tumor Necrosis Factor-Induced Inflammatory Shock.” BMC PHYSIOLOGY 14. doi:10.1186/s12899-014-0005-1.
- Vancouver
- 1.Vandendriessche B, Goethals A, Simats A, Van Hamme E, Brouckaert P, Cauwels A. MAPK-activated protein kinase 2-deficiency causes hyperacute tumor necrosis factor-induced inflammatory shock. BMC PHYSIOLOGY. 2014;14.
- IEEE
- [1]B. Vandendriessche, A. Goethals, A. Simats, E. Van Hamme, P. Brouckaert, and A. Cauwels, “MAPK-activated protein kinase 2-deficiency causes hyperacute tumor necrosis factor-induced inflammatory shock,” BMC PHYSIOLOGY, vol. 14, 2014.
@article{6849087,
abstract = {{Background: MAPK-activated protein kinase 2 (MK2) plays a pivotal role in the cell response to (inflammatory) stress. Among others, MK2 is known to be involved in the regulation of cytokine mRNA metabolism and regulation of actin cytoskeleton dynamics. Previously, MK2-deficient mice were shown to be highly resistant to LPS/D-Galactosamine-induced hepatitis. Additionally, research in various disease models has indicated the kinase as an interesting inhibitory drug target for various acute or chronic inflammatory diseases.
Results: We show that in striking contrast to the known resistance of MK2-deficient mice to a challenge with LPS/D-Gal, a low dose of tumor necrosis factor (TNF) causes hyperacute mortality via an oxidative stress driven mechanism. We identified in vivo defects in the stress fiber response in endothelial cells, which could have resulted in reduced resistance of the endothelial barrier to deal with exposure to oxidative stress. In addition, MK2-deficient mice were found to be more sensitive to cecal ligation and puncture-induced sepsis.
Conclusions: The capacity of the endothelial barrier to deal with inflammatory and oxidative stress is imperative to allow a regulated immune response and maintain endothelial barrier integrity. Our results indicate that, considering the central role of TNF in pro-inflammatory signaling, therapeutic strategies examining pharmacological inhibition of MK2 should take potentially dangerous side effects at the level of endothelial barrier integrity into account.}},
articleno = {{5}},
author = {{Vandendriessche, Benjamin and Goethals, An and Simats, Alba and Van Hamme, Evelien and Brouckaert, Peter and Cauwels, Anje}},
issn = {{1472-6793}},
journal = {{BMC PHYSIOLOGY}},
keywords = {{Inflammatory shock,MK2,Tumor necrosis factor,Reactive oxygen species,Actin cytoskeleton,Endothelial permeability,Cecal ligation and puncture}},
language = {{eng}},
pages = {{10}},
title = {{MAPK-activated protein kinase 2-deficiency causes hyperacute tumor necrosis factor-induced inflammatory shock}},
url = {{http://doi.org/10.1186/s12899-014-0005-1}},
volume = {{14}},
year = {{2014}},
}
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