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Characterization of the angiomodulatory effects of Interleukin 11 cis- and trans-signaling in the retina
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Characterization of the angiomodulatory effects of Interleukin 11 cis- and trans-signaling in the retina
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Journal Article
Characterization of the angiomodulatory effects of Interleukin 11 cis- and trans-signaling in the retina
2024
Overview
Background
The IL-6 cytokine family, with its crucial and pleiotropic intracellular signaling pathway STAT3, is a promising target for treating vasoproliferative retinal diseases. Previous research has shown that IL-6 cis-signaling (via membrane-bound receptors) and trans-signaling (via soluble receptors) can have distinct effects on target cells, leading to their application in various disease treatments. While IL-6 has been extensively studied, less is known about the angiogenic effects of IL-11, another member of the IL-6 family, in the retina. Therefore, the aim of this study was to characterize the effects of IL-11 on retinal angiogenesis.
Main text
In vitreous samples from proliferative diabetic retinopathy (PDR) patients, elevated levels of IL-11Rα, but not IL-11, were detected. In vitro studies using vascular endothelial cells revealed distinct effects of cis- and trans-signaling: cis-signaling (IL-11 alone) had antiangiogenic effects, while trans-signaling (IL-11 + sIL-11Rα) had proangiogenic and pro-migratory effects. These differences can be attributed to their individual signaling responses and associated transcriptomic changes. Notably, no differences in cis- and trans-signaling were detected in primary mouse Müller cell cultures. STAT3 and STAT1 siRNA knockdown experiments revealed opposing effects on IL-11 signaling, with STAT3 functioning as an antiproliferative and proapoptotic player while STAT1 acts in opposition to STAT3. In vivo, both IL-11 and IL-11 + sIL-11Rα led to a reduction in retinal neovascularization. Immunohistochemical staining revealed Müller cell activation in response to treatment, suggesting that IL-11 affects multiple retinal cell types in vivo beyond vascular endothelial cells.
Conclusions
Cis- and trans-signaling by IL-11 have contrasting angiomodulatory effects on endothelial cells in vitro. In vivo, cis- and trans-signaling also influence Müller cells, ultimately determining the overall angiomodulatory impact on the retina, highlighting the intricate interplay between vascular and glial cells in the retina.
Publisher
BioMed Central,BioMed Central Ltd,BMC
Subject
/ Animals
/ Biomedical and Life Sciences
/ Diabetic Retinopathy - metabolism
/ Diabetic Retinopathy - pathology
/ Endothelial Cells - drug effects
/ Endothelial Cells - metabolism
/ Female
/ Humans
/ Interleukin-11 - pharmacology
/ Male
/ Mice
/ Neuroinflammation in the Retina
/ Scientific equipment and supplies industry
/ Signal Transduction - drug effects
/ Signal Transduction - physiology
/ STAT3
