Soluble IL-6 Receptor in Vitreous Fluid of Patients with Proliferative Diabetic Retinopathy

Kawashima, Masayuki; Shoji, Jun; Nakajima, Masami; Kamura, Yumi; Sato, Yukihiro

doi:10.1007/s10384-006-0411-4

Cited by 16 publications

(14 citation statements)

References 21 publications

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“…These levels were initially measured using radioimmunoassay techniques, 1 after which enzyme-linked immunosorbent assay methods became widely used. 2,5,7,14,38 Presently, multiplex bead assays, which determine the levels of multiple cytokines at the same time in a single sample, have become practical for use. 39 FGF, fibroblast growth factor; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; PDGFbb, platelet-derived growth factor; RANTES, regulated on activation, T-cell expresses and secreted; TNF-a, tumor necrosis factor a.…”

Section: Discussionmentioning

confidence: 99%

Effects of Intravitreal Injection of Bevacizumab on Inflammatory Cytokines in the Vitreous With Proliferative Diabetic Retinopathy

Suzuki

Yokoi

et al. 2014

Retina

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Preoperative IVB reduced not only the intravitreal vascular endothelial growth factor level but also the intravitreal levels of other inflammatory cytokines, including IL-1RA, IL-5, IL-10, IL-12, IL-13, and interferon γ. These results indicate the interaction of some cytokines in the vitreous fluid of proliferative diabetic retinopathy patients and suggest the possibility that preoperative IVB may not only reduce vascular proliferation by its direct antivascular endothelial growth factor effect but also modulate the inflammatory response through putative cytokine networks. None of the other cytokines examined were elevated after IVB.

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Section: Discussionmentioning

confidence: 99%

Effects of Intravitreal Injection of Bevacizumab on Inflammatory Cytokines in the Vitreous With Proliferative Diabetic Retinopathy

Suzuki

Yokoi

et al. 2014

Retina

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“…35 Serum and vitreous levels of IL-6 may have a role in PDR. 3,5,8,[14][15][16]21,27 Further, the significant correlation between increased vitreous VEGF and EDN1 in PDR considers the fact of the stimulatory interaction between VEGF and EDN1 on each expression, which may play important roles in concomitant proliferation of endothelial and smooth muscle cells in the vascular wall. 36 The retinal angiogenesis and growth of fibrotic tissue can cause vitreous hemorrhage and traction retinal detachment, and then cause the severe vision loss in the patients with diabetic retinopathy.…”

Section: Current Eye Researchmentioning

confidence: 95%

“…34 VEGF was found elevated in the vitreous of our patients with PDR, which is in accordance with previous findings. [13][14][15][16]25,26,28,34 IL6 is a multifunctional cytokine that indirectly causes an increase in vascular permeability and neovascularization by inducing the expression of VEGF, and also directly increases endothelial cell permeability in vitro by rearranging actin filaments and by changing the shape of endothelial cells. 35 Serum and vitreous levels of IL-6 may have a role in PDR.…”

Section: Current Eye Researchmentioning

confidence: 99%

“…Interleukins play an important role in the regulation of immune mechanisms. [3][4][5][6][7][8][9][10][11][12][13][14][15][16] ABSTRACT Objective: Inflammatory reaction has been shown to involve the progress of type 2 (non-insulin-dependent) diabetes. We, therefore, examined the effects of inflammatory cytokines and angiogenic factors in the pathogenesis of proliferative diabetic retinopathy (PDR) in type 2 diabetes.…”

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confidence: 99%

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Role of Intravitreal Inflammatory Cytokines and Angiogenic Factors in Proliferative Diabetic Retinopathy

Zhou

Wang

Xia

2012

Current Eye Research

143

120

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The inflammatory cytokines and angiogenic factors IL1B, IL6, IL8, CCL2, EDN1, VEGF, and TNF are increased in the vitreous of PDR patients without an increase in IL-10. These results add support to the role of inflammatory cytokines and angiogenic factors in the genesis of PDR. Understanding the implication of these cytokines may provide diagnostic tools and therapeutic targets for treatment and prevention of PDR.

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“…In addition, higher levels of sIL-6R were found in the serum and vitreous fluid of patients with proliferative DR. Furthermore, the levels of sIL-6R had a significant correlation with VEGF levels in the vitreous fluid (34). …”

Section: Introductionmentioning

confidence: 99%

miR-146a suppresses STAT3/VEGF pathways and reduces apoptosis through IL-6 signaling in primary human retinal microvascular endothelial cells in high glucose conditions

Steinle

2017

Vision Research

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microRNA (miRNA) play critical roles in the pathological processes of diabetic retinopathy, including inflammatory responses, insulin signaling, and angiogenesis. In addition to their regulatory functions on gene expression, miRNA is considered as a potential therapeutic target, as well as a diagnostic marker for many diseases. Our understanding on the pathological mechanisms underlying diabetic retinopathy is still incomplete and additional investigations are required to develop novel therapeutic strategies. The aim of this study was to investigate our hypothesis that miR-146a plays a role in suppressing pro-inflammatory pathways, involving STAT3 and VEGF, through regulating IL-6 signaling to reduce apoptosis of human retinal endothelial cells (REC) in high glucose conditions. Human REC were cultured in normal (5mM) glucose or high glucose medium (25 mM) for 3 days. We performed transfections on REC with miRNA mimics (hsa-miR-146a-5p). Overexpression of miR-146a reduced IL-6 levels, STAT3 phosphorylation, and VEGF levels in REC cultured in high glucose. Cellular apoptosis was decreased in REC overexpressing miR-146a, as demonstrated by the inhibition of DNA fragmentation. More importantly, we demonstrated that the regulatory role of miR-146a on STAT3/VEGF and apoptosis was mediated by IL-6 receptor signaling in REC. Overall, we report that miR-146a suppressed IL-6 signaling, leading to reduced levels of STAT3 and VEGF in REC in high glucose conditions, leading to decreased apoptosis. The outcome suggests that miR-146a is a potential molecular target for inhibiting inflammation and apoptosis in the diabetic retina through the suppression of the IL-6-mediated STAT3/VEGF pathway.

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Soluble IL-6 Receptor in Vitreous Fluid of Patients with Proliferative Diabetic Retinopathy

Abstract: We conclude that the level of sIL-6R in vitreous fluid can be considered as a biomarker of PDR.

Cited by 16 publications

References 21 publications

Effects of Intravitreal Injection of Bevacizumab on Inflammatory Cytokines in the Vitreous With Proliferative Diabetic Retinopathy

Effects of Intravitreal Injection of Bevacizumab on Inflammatory Cytokines in the Vitreous With Proliferative Diabetic Retinopathy

Role of Intravitreal Inflammatory Cytokines and Angiogenic Factors in Proliferative Diabetic Retinopathy

miR-146a suppresses STAT3/VEGF pathways and reduces apoptosis through IL-6 signaling in primary human retinal microvascular endothelial cells in high glucose conditions

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