Cytokine angiogenic activity

Neovascularization in artherosclerotic lesions may be regulated by VEGF, as this factor is over-expressed by different cells in the plaque tissue [40-42]. The increased serum levels of VEGF that correlate with disease activity in patients with Crohn s disease and ulcerative colitis, indicate a role for this cytokine in promoting inflammation. Most likely, increased vascn-lar permeability and/or wound healing via its pro-angiogenic activity are the basis for this effect [43]. 

Birnbaum T, Roider J, Schankin CJ, Padovan CS, Schichor C, Goldbrunner R, Straube A (2007) Malignant gliomas actively recruit bone marrow stromal cells by secreting angiogenic cytokines. J Neurooncol 83 241-247... 

In most, if not all, chronic inflammatory diseases endothelial cells are prominently involved in the disease process. This is demonstrated by an increased expression of adhesion molecules and production of cytokines, and their pro-angiogenic behaviour. This leads to continuous recruitment of leucocytes into the inflamed area, without (detectable) antigen present in the affected tissue, resulting in a vicious circle of tissue damage and leucocyte recruitment. Targeting inhibitory agents (in)to the endothelial cell may interrupt in this process by controlling the activation status of this cell type. 

Inhibitors of IkBo phosphorylation have been described which irreversibly inhibit cytokine-induced phosphorylation without affecting constitutive phosphorylation. One such compound (Bay 11-7083 ((E)3-[4-f-butylphenyl)-sulfonyl]-2-propenenitrile)) was found to be effective in two animal models of inflammation after intraperitoneal administration [89]. In addition to the effect it has on the expression of adhesion molecules in pro-inflammatory responses, inhibition of the transcription factor NFkB will also have an effect on angiogenesis. Endothelial cells can produce growth factors and cytokines which have pro-angiogenic effects. Some of these factors, e.g. IL-8, TNFa and MCP-1 are known to be produced via NFkB-mediated endothelial cell activation [90,91]. The importance of NFKB-mediated responses in pro-angiogenic endothelium was reflected in studies in which the NFkB inhibitor PDTC decreased retinal neovascularization in the eye of mice [92]. 

Figure 12-9 Corneal acute inflammation./wset Corneal epithelial cells that have been activated by proinflammatory molecules. Activated cytokines disperse though the stroma and in the limbal vessels. Proteases (represented by the large scissors ) can damage the basement membrane, leading to growth factor and angiogenic factor release. (From McDermott AM, Perez V, Huang AJ, et al. Pathways of corneal and ocular surface inflammation a perspective from the Cullen Symposium, Ocul Surf 2005 0ct 3(4 Suppl) S131-138.)...

Alternatively, the virus could use ECRF3 to exploit the cytokine functions of its chemokine ligands to ensure a cytosolic milieu that has been optimally conditioned for replication or for the establishment of latency. In this regard, IL-8 and GROa are angiogenic in certain in vivo models, including the rat cornea neovascularization model (67), and are chemotactic for endothelial cells in vitro, although the receptor responsible for this activity has not been defined. 

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