Role of Angiogenic cytokines

Angiogenic cytokines review

Angiogenesis, the formation of new blood vessels from existing vasculature, is fundamental for a variety of physiological and pathological processes including tumor growth andmetastasis. Amsong these factors, vascular endothelial growth factor (VEGF) and transforming growth factor- β1 (TGF-β1) are preeminent glioblastoma-associated multifunctional cytokines that stimulate migration, tissue invasion and angiogenesis.

VEGF is a secreted heparin-binding glycoprotein and one of the most potent endothelial cell-specific mitogens. It is known to play a key role in tumor angiogenesis. TGF-β1 overexpression has been associated with several cancers and correlates with tumor progression, angiogenesis and poor prognosis.

IL-20, an anti-angiogenic cytokine that inhibits COX-2 expressions

Non-small cell lung cancer (NSC LC) cells frequently constitutively overexpress cyclooxy genase-2 (COX -2), a key enzyme in prostaglandins biosynthesis. Because COX-2 overexpression and subsequent prostaglandin-E2(PGE2) production have been implicated inconferring the malignant and metastatic phenotypes, investigations have focused on delineating the mechanisms mediating tumor COX-2 overexpression. Tumor promoters, mutations, cytokines, and growth factors have been shown to induce COX-2 and PGE2 production. IL-10 has the capacity to down-regulate COX-2 in cells such as monocytes. In contrast, IL-10-mediated regulation of COX-2 is not operative in NSCLC. Thus, although IL-10 is the predominant Th2 cytokine in the lung cancer microenvironment, it does not function to control tumor-COX-2 expression. A family of IL-10-related cytokines with limited primary sequence identity but sharing structural homology to IL-10 has been identified. Among these cytokines is IL-20, an anti-angiogenic cytokine. Receptors mediating IL-20 cellular responses have been detected in normal lung tissue. However, this anti-angiogenic cytokine biological function in the pulmonary microenvironment is still un-known. It is the first time that IL -20 inhibits COX- 2/PGE2 production in HBEC and to a lesser degree in NSCLC, and limits COX- 2-mediated angiogenesis is in vitro. Reduced IL-20 expression and efficiency of IL-20 to regulate COX-2/PGE2 in NSCLC cells may thus contribute to maintenance of elevated COX- 2/PGE2 and promotion of tumor angiogenesis.

IFN-γ acts as anti-angiogenic cytokine in the human cornea

Inflammatory processes within the cornea are known to be associated with corneal neovascularization (CN). Corneal avascularity, regulated by VEGF-A and sVEGF-R1 (sFlt-1), primarily contributes to transparency. In addition, IFN-γ, TNF-α, IL-1 a, IL-1 β, and TGF-β were detected in epithelial and stromal cell layers in neovascularized human cornea. TNF-α and IL-1 induced VEGF-A secretion by corneal fibroblasts (HCRF) and this was inhibited significantly by IFN-γ which acts as anti-angiogenic cytokine cytokines.

Cytokine molecules related

IFN Receptor

IL10 Family Receptor

TGF beta Family Receptor

References

1, Napoleone Ferrara, et al.The biology of VEGF and its receptor.
2,Vijay K. Kommineni, et al. IFN-γ acts as anti-angiogenic cytokine in the human cornea by regulating the expression of VEGF-A and sVEGF-R1.V.K. Kommineni et al. / Biochemical and Biophysical Research Communications 374 (2008) 479–484
3, Nathalie Heuze´ -Vourc'h, et al. IL-20, an anti-angiogenic cytokine that inhibits COX-2 expression.Biochemical and Biophysical Research Communications 333 (2005) 470–475