Interleukin 6 Induces the Expression of Vascular Endothelial Growth Factor

Cohen, Tzafra; Nahari, Dorit; Cerem, Lea Weiss; Neufeld, Gera; Levi, Ben‐Zion

doi:10.1074/jbc.271.2.736

Cited by 927 publications

(572 citation statements)

References 49 publications

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“…2,3 It has been suggested that IL-6 may indirectly induce angiogenesis by stimulating VEGF expression, as occurs with the induction of VEGF mRNA by hypoxia. 9 It has been suggested that induction of VEGF mRNA probably occurs through transcriptional regulation, so previous reports combined with our results would indicate that IL-6 may affect neovascularization and the progression of PDR after vitreous surgery by upregulating expression of VEGF. However, further investigations will be needed to clarify the ocular interactions between IL-6 and VEGF, as well as the role of IL-6 during neovascularization in PDR patients and after vitreous surgery.…”

Section: Discussionsupporting

confidence: 72%

“…All three fundus parameters (NVE, NVD, and FPE) reflect retinal neovascularization, while VEGF and IL-6 are involved in the onset and progression of new vessel formation. 1,2,9 It was suggested that the additional laser was needed to reduce the activity of new vessel formation during surgery in the advanced cases. Therefore, active neovascularization is associated with the progression of PDR.…”

Section: Eyementioning

confidence: 99%

“…7 IL-6 is related to hyperglycemia and hypoxia, 8 and it is considered to be an indirect inducer of angiogenesis that acts through the induction of VEGF. 9 In an attempt to predict the outcome of vitreous surgery in PDR patients, we investigated whether vitreous and plasma levels of VEGF and/or IL-6 were correlated with the results, that is, whether it was possible to predict the outcome of surgery by measuring VEGF and IL-6 in the vitreous fluid obtained at operation along with assessment of fundus findings.…”

Section: Introductionmentioning

confidence: 99%

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Risk evaluation of outcome of vitreous surgery based on vitreous levels of cytokines

Funatsu

Yamashita

Mimura³

et al. 2006

Eye

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Section: Discussionsupporting

confidence: 72%

Section: Eyementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Risk evaluation of outcome of vitreous surgery based on vitreous levels of cytokines

Funatsu

Yamashita

Mimura³

et al. 2006

Eye

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“…Although previous studies have confirmed that IL-6 is important in both physiological and pathological angiogenesis (Cohen et al, 1996;Mahnke et al, 2000), IL-6 has recently received more attention as a critical cytokine implicated in the angiogenesis of several human cancers, including cervical cancer, basal cell carcinoma, glioma, gastric carcinoma and mesothelioma (Wei et al, 2003;Huang et al, 2004;Jee et al, 2004;Loeffler et al, 2005;Adachi et al, 2006;Saidi et al, 2009). Strikingly, these investigations provide evidence that IL-6 may promote VEGF-induced tumor angiogenesis.…”

Section: Discussionmentioning

confidence: 93%

Integrin-linked kinase regulates melanoma angiogenesis by activating NF-κB/interleukin-6 signaling pathway

et al. 2011

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Integrin-linked kinase (ILK) is a highly conserved serinethreonine protein kinase involved in cell-extracellular matrix interactions, cytoskeletal organization and cell signaling. Overexpression of ILK in epithelial cells leads to anchorage-independent growth with increased cell cycle progression. Previously, we have shown that ILK upregulation strongly correlates with melanoma progression, invasion and inversely correlates with 5-year survival of melanoma patients. However, the molecular mechanism by which ILK enhances melanoma progression is currently unknown. In the present study, we found that proangiogenic molecule interleukin-6 (IL-6) is the downstream target of ILK in melanoma cells. ILK overexpression increased IL-6, whereas silencing of ILK suppressed IL-6 expression at both messenger RNA and protein levels. ILK also altered the activity and subcellular localization of nuclear factor-kappaB (NF-jB) subunit p65. We further found that ILK enhanced the IL-6 gene transcription by promoting the binding of NF-kB p65 to IL-6 promoter. Moreover, ILK overexpression in melanoma cells enhanced the tube-forming ability of endothelial cells in vitro and microvessel formation in vivo. ILK-induced tube and blood vessel formation of endothelial cells was significantly reduced upon IL-6 inhibition in ILK-overexpressing melanoma cells. To delineate the mechanism by which ILK-induced IL-6 production can enhance angiogenesis, further analysis of the downstream targets of IL-6 signaling showed an increased activity of the signal transducer and activator of transcription 3 (STAT3) in ILK-overexpressing cells. As STAT3 binds to vascular endothelial growth factor (VEGF) promoter, we found that VEGF levels were elevated in ILK-overexpressing cells and declined upon transfection of IL-6 small interfering RNA, suggesting that ILK may regulate VEGF expression through IL-6 pathway by activating STAT3.

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“…Transcription of VEGF mRNA is enhanced by a variety of factors, including platelet-derived growth factor (PDGF)-BB, basic ®broblast growth factor, keratinocyte growth factor, epidermal growth factor, tumor necrosis factor a, transforming growth factor (TGF) a, TGFb1, interleukin-1b, and interleukin 6, in a variety of cultured cells (Finkenzeller et al, 1992;Brogi et al, 1994;Frank et al, 1995;Detmar et al, 1994;Pertovaara et al, 1994;Li et al, 1995;Cohen et al, 1996). Enhanced VEGF expression has been reported upon activation of protein kinase C by tumor promoters, and in cells harbouring activated oncogenes, such as ras, raf, and src (Grugel et al, 1995;Rak et al, 1995;Mukhopadhyay et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Sp1 recognition sites in the proximal promoter of the human vascular endothelial growth factor gene are essential for platelet-derived growth factor-induced gene expression

Finkenzeller

Sparacio

Technau³

et al. 1997

Oncogene

182

169

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Stimulation of NIH3T3 cells with platelet-derived growth factor (PDGF)-BB enhances expression of vascular endothelial growth factor (VEGF), an endothelial cell-speci®c mitogen and a key mediator of tumor angiogenesis. Here, we identi®ed cis-acting VEGF promoter elements and trans-acting factors which are involved in PDGF-stimulated VEGF expression. By 5'-deletion and transient transfection analysis, a G+C-rich region at 785 to 750 of the human VEGF promoter was shown to be necessary and su cient for both PDGF inducible and basal expression. The region contains three potential recognition sites for Sp1 transcription factors, which overlap with two Egr-1 sites. Mutations that abolish the ability of Sp1 to interact with the VEGF promoter element also abrogate expression induced by PDGF. Mutations of the potential Egr-1 binding sites did not a ect PDGF responsiveness. Gel shift and antibody supershift analyses showed that Sp1 and Sp3 interact constitutively with the VEGF promoter element. Our data strongly suggest that enhanced VEGF gene expression in PDGF-induced NIH3T3 cells is mediated by Sp1 and/or Sp3 transcription factors bound to the 785 to 750 promoter region of the VEGF gene.

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Interleukin 6 Induces the Expression of Vascular Endothelial Growth Factor

Cited by 927 publications

References 49 publications

Risk evaluation of outcome of vitreous surgery based on vitreous levels of cytokines

Risk evaluation of outcome of vitreous surgery based on vitreous levels of cytokines

Integrin-linked kinase regulates melanoma angiogenesis by activating NF-κB/interleukin-6 signaling pathway

Sp1 recognition sites in the proximal promoter of the human vascular endothelial growth factor gene are essential for platelet-derived growth factor-induced gene expression

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