May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
VEGF and TNF alpha Induce MCP-1 Production via NADPH Oxidase, p38 MAPK, and Sphingosine Kinase
Author Affiliations & Notes
  • W. Zhang
    Vascular Biology Center, Medical College of Georgia, Augusta, Georgia
  • R. B. Caldwell
    Vascular Biology Center, Medical College of Georgia, Augusta, Georgia
  • Footnotes
    Commercial Relationships W. Zhang, None; R.B. Caldwell, None.
  • Footnotes
    Support NIH Grant EY04618, EY11766; VA
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1373. doi:https://doi.org/
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      W. Zhang, R. B. Caldwell; VEGF and TNF alpha Induce MCP-1 Production via NADPH Oxidase, p38 MAPK, and Sphingosine Kinase. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1373. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose:: Monocyte chemoattractant protein (MCP)-1 is a potent chemotactic protein for monocytes, memory T cells and microglia in the context of inflammation. Up-regulation of the expression of MCP-1 has been implicated in the process of retina inflammation in diabetic retinopathy and uveitis. VEGF and the proinflammatory cytokine TNF alpha have been shown to play critical roles in diabetic retinopathy and uveitis.This study was undertaken to understand the mechanisms of MCP-1 up-regulation during vascular inflammation induced by VEGF and TNF alpha.

Methods:: The secretion of MCP-1 from cultured endothelial cells was measured by ELISA. The signaling events for VEGF and TNF induced MCP-1 up-regulation were investigated by using specific inhibitors of protein kinases.

Results:: Inhibition of NADPH oxidase, p38 MAPK, and sphingosine kinase remarkably attenuated both VEGF and TNF alpha-induced MCP-1 up-reguation. On the other hand, inhibtion of Rho kinase, PKC alpha, and PKC beta only blocked VEGF-induced MCP-1 up-regulation but had little or no effect on TNF alpha-induced MCP-1 production.

Conclusions:: VEGF and TNF alpha share common pathway to induce MCP-1 production in endothelial cells, which invovles NADPH oxidase, p38 MAPK and sphingosine kinase. Inhibition of these kinases may provide therapeutic benefit for the treatment of retina vascular inflammation.

Keywords: inflammation • vascular cells • signal transduction 
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