Pro-inflammatory angiogenesis is mediated by p38 MAP kinase.

Raja Shekhar Gangaraju, Malgorzata Kamocka, Abby Marin, Mark A. Suckow, William R. Wolter, Sunil Badve, Aravind Raj Sanjeevaiah, Kevin Pumiglia, Elliot Rosen, Matthias Clauss

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Chronic inflammation is tightly linked to diseases associated with endothelial dysfunction including aberrant angiogenesis. To better understand the endothelial role in pro-inflammatory angiogenesis, we analyzed signaling pathways in continuously activated endothelial cells, which were either chronically exposed to soluble TNF or the reactive oxygen species (ROS) generating H2O2, or express active transmembrane TNF. Testing in an in vitro capillary sprout formation assay, continuous endothelial activation increased angiogenesis dependent on activation of p38 MAP kinase, NADPH oxidase, and matrix metalloproteinases (MMP). p38 MAP kinase- and MMP-9-dependent angiogenesis in our assay system may be part of a positive feed forward autocrine loop because continuously activated endothelial cells displayed up-regulated ROS production and subsequent endothelial TNF expression. The pro-angiogenic role of the p38 MAP kinase in continuously activated endothelial cells was in stark contrast to the anti-angiogenic activity of the p38 MAP kinase in unstimulated control endothelial cells. In vivo, using an experimental prostate tumor, pharmacological inhibition of p38 MAP kinase demonstrated a significant reduction in tumor growth and in vessel density, suggesting a pro-angiogenic role of the p38 MAP kinase in pathological angiogenesis in vivo. In conclusion, our results suggest that continuous activation of endothelial cells can cause a switch of the p38 MAP kinase from anti-angiogenic to pro-angiogenic activities in conditions which link oxidative stress and autocrine TNF production.

Original languageEnglish (US)
Pages (from-to)800-808
Number of pages9
JournalJournal of Cellular Physiology
Volume226
Issue number3
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

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p38 Mitogen-Activated Protein Kinases
Endothelial cells
Endothelial Cells
Chemical activation
Tumors
Assays
Reactive Oxygen Species
Pathologic Neovascularization
Oxidative stress
NADPH Oxidase
Matrix Metalloproteinase 9
Matrix Metalloproteinases
Prostate
Neoplasms
Oxidative Stress
Switches
Pharmacology
Inflammation
Testing
Growth

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Gangaraju, R. S., Kamocka, M., Marin, A., Suckow, M. A., Wolter, W. R., Badve, S., ... Clauss, M. (2011). Pro-inflammatory angiogenesis is mediated by p38 MAP kinase. Journal of Cellular Physiology, 226(3), 800-808. https://doi.org/10.1002/jcp.22404

Pro-inflammatory angiogenesis is mediated by p38 MAP kinase. / Gangaraju, Raja Shekhar; Kamocka, Malgorzata; Marin, Abby; Suckow, Mark A.; Wolter, William R.; Badve, Sunil; Sanjeevaiah, Aravind Raj; Pumiglia, Kevin; Rosen, Elliot; Clauss, Matthias.

In: Journal of Cellular Physiology, Vol. 226, No. 3, 01.01.2011, p. 800-808.

Research output: Contribution to journalArticle

Gangaraju, RS, Kamocka, M, Marin, A, Suckow, MA, Wolter, WR, Badve, S, Sanjeevaiah, AR, Pumiglia, K, Rosen, E & Clauss, M 2011, 'Pro-inflammatory angiogenesis is mediated by p38 MAP kinase.', Journal of Cellular Physiology, vol. 226, no. 3, pp. 800-808. https://doi.org/10.1002/jcp.22404
Gangaraju, Raja Shekhar ; Kamocka, Malgorzata ; Marin, Abby ; Suckow, Mark A. ; Wolter, William R. ; Badve, Sunil ; Sanjeevaiah, Aravind Raj ; Pumiglia, Kevin ; Rosen, Elliot ; Clauss, Matthias. / Pro-inflammatory angiogenesis is mediated by p38 MAP kinase. In: Journal of Cellular Physiology. 2011 ; Vol. 226, No. 3. pp. 800-808.
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