Focus on Molecules: Interleukin-1: A master regulator of the corneal response to injury

Wilson, Steven E.; Esposito, Andrew C.

doi:10.1016/j.exer.2009.02.011

Cited by 43 publications

(45 citation statements)

References 3 publications

(4 reference statements)

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“…This response is a critical determinant of the outcomes of corneal surgical procedures, especially photorefractive keratectomy and other corneal surface ablation procedures, in addition to scarring that may occur after injury, infection and other surgeries [14]. It was shown that the proinflammatory cytokine IL-1β is released by corneal epithelium during injuries [38, 39]. However, our in vitro study showed that KYN affects its release neither by human corneal nor conjunctival epithelial cells.…”

Section: Discussioncontrasting

confidence: 43%

Examination of Kynurenine Toxicity on Corneal and Conjunctival Epithelium: In vitro and in vivo Studies

Matysik-Woźniak

Turski²,

Turska

et al. 2019

Ophthalmic Res

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Kynurenine (KYN) is a metabolite of tryptophan, proposed for the treatment of corneal diseases. Our goal was to evaluate the effects of KYN on normal human corneal and conjunctival epithelial cells in vitro and the re-epithelization of corneal erosion in rabbits. In our study, we used corneal (10.014 pRSV-T) and conjunctival (HC0597) epithelium cell cultures. KYN was applied at a concentration range of 1–100 µM for 24 and 48 h. We examined the effects on cellular metabolism, viability, interleukin-1β (IL-1β), IL-6, IL-10 secretion, cytoskeleton organization and transwell migration ability. Following a bilateral corneal de-epithelialization, the rabbits received drops containing 1% KYN and a saline solution to the contralateral control eye, 5 times daily. Digital images were analyzed using the EPCO 2000 software. The metabolic activity of cells was slightly decreased by KYN in the corneal but not in the conjunctival epithelium. The viability of both epithelia was improved by KYN; it caused alterations in the secretion of IL-6 and IL-10 but not IL-1β. It had no impact on both epithelia morphology and the organization of the cellular cytoskeleton. KYN stimulated the formation of pseudopodia projections in both epithelia in vitro, which may be important in terms of wound healing. However, there were no differences in the re-epithelization rate in vivo. At the tested concentrations, KYN was not toxic for the corneal and the conjunctival epithelium in vitro and did not affect corneal re-epithelization in rabbits in vivo. Our results suggest that KYN may be taken into consideration for the treatment of ocular disorders.

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Section: Discussioncontrasting

confidence: 43%

Examination of Kynurenine Toxicity on Corneal and Conjunctival Epithelium: In vitro and in vivo Studies

Matysik-Woźniak

Turski²,

Turska

et al. 2019

Ophthalmic Res

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“…However, West-Mays and coworkers (1997) demonstrated that corneal fibroblasts derived from keratocytes during corneal wound healing are activated to produce autocrine IL-1α. Recently, it was demonstrated that, at one month after PRK, stromal cells in the anterior stroma produce IL-1α (Wilson and Esposito, in press). It’s as yet unknown whether these IL-1α expressing-cells are corneal fibroblasts, myofibroblasts, keratocytes or other cells, or how long this stromal IL-1 production persists following injury, but if expression is maintained in the stroma for many months or years it could provide a source for myofibroblast regulation in vivo .…”

Section: Discussionmentioning

confidence: 99%

Corneal myofibroblast viability: Opposing effects of IL-1 and TGF β1

Kaur

Chaurasia

Agrawal

et al. 2009

Experimental Eye Research

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The purpose of this study was to test the effect of corneal epithelial scrape on myofibroblasts associated with haze and elucidate the effect of interleukin-1 and transforming growth factor beta-1 on corneal stromal myofibroblasts viability and death in vitro. Corneal epithelial scrape was performed in rabbit eyes with severe haze at one month after -9 diopter photorefractive keratectomy. Corneas were processed for immunocytochemistry for myofibroblast marker α-smooth muscle actin (α-SMA) and the TUNEL assay to detect apoptosis. Rabbit corneal fibroblasts were cultured with 2 ng/ml of transforming growth factor-β1 (TGF β1) to induce myofibroblast differentiation confirmed by monitoring α-SMA expression. Fluorescence-based TUNEL assay was performed to analyze the apoptotic response of myofibroblasts to IL-1α or IL-1β in the presence or absence of TGFβ1. Dose response experiments were performed after withdrawal of TGFβ1 and exposure to 1, 5, or 10 ng/ml of IL-1α or IL-1β for 1 hour. Subsequent experiments were performed with myofibroblasts exposed to 5 ng/ml IL-1α or IL-1β in conjunction with 0, 1, 5, or 10 ng/ml TGFβ1. Corneal epithelial scrape with a scalpel blade produced myofibroblast apoptosis. Exposure to TGF β1 in vitro resulted in greater than 99% transformation of corneal fibroblasts to α-SMA+ myofibroblasts. There was a statistically significant dose dependent increase in the percentage of TUNEL+ cells with either IL-1α or IL-1β initiated at concentrations as low as 1 ng/ml. For example, after withdrawal of TGFβ1, the % TUNEL+ cells at 1 hour after exposure to IL-1α increased significantly with increasing concentration (0 ng/ml, 2.4±0.8 [S.E.M.] %; 1 ng/ml, 15.4±1.8%; 5 ng/ml, 47.4±3.9%; or 10 ng/ml, 70.3±3.2%). Similar results were obtained with IL-1β. The differences between the means of apoptotic myofibroblasts for the different concentrations of cytokine for either IL-1α or IL-1β were significantly different (ANOVA p<0.001). When myofibroblasts were exposed to 5 ng/ml IL-1α or IL-1β, the % TUNEL+ cells at 1 hour were reduced in a significant dose dependent manner when TGF β1 at a concentration of 5 ng/ml or 10 ng/ml was present in the medium (ANOVA p<0.01). IL-1α or IL-1β triggers the death of myofibroblasts in vitro and TGF β1 reduces the IL-1 effect on cell death. TGF β1 and IL-1 have opposing effects on myofibroblast viability and likely interact to modulate haze generation after corneal injury.

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“…30 In similar manner as it was observed in an inflamed skin, injured corneal epithelial cells release IL-1β and, in IL-1β-dependent manner, elicit strong immune response during the early stage of corneal injury and dry eye syndrome (DED). 31,32 The strongest expression of IL-1Ra was noticed in the superficial apical layer of corneal epithelium where IL-1Ra attenuates ongoing inflammation by suppressing IL-1β:IL-1RI signaling in cornealinfiltrated immune cells. 33 Therefore, IL-1Ra represents an endogenous mechanism of protection against epithelial-and tear-derived IL-1β in the injured eyes.…”

Section: Beneficial Effects Of Msc-derived Il-1ra In the Repair Of mentioning

confidence: 99%

The role of Interleukin 1 receptor antagonist in mesenchymal stem cell‐based tissue repair and regeneration

et al. 2019

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Interleukin (IL)‐1 receptor antagonist (IL‐1Ra), a naturally occurring antagonist of IL‐1α/IL‐1β signaling pathways, has been attributed to the immunosuppressive effects of mesenchymal stem cells (MSCs). MSCs, in IL‐1Ra‐dependent manner, suppressed production of IL‐1β in dermal macrophages, induced their polarization in anti‐inflammatory M2 phenotype, attenuated antigen‐presenting properties of dendritic cells (DCs), and promoted expansion of immunosuppressive T regulatory cells in the skin, which resulted in enhanced repair of the nonhealing wounds. Reduced activation of inflammasome and suppressed production of IL‐1β in macrophages were mainly responsible for beneficial effects of MSC‐derived IL‐1Ra in alleviation of acute lung injury, dry eye syndrome, and corneal injury. Through the production of IL‐1Ra, MSCs reduced migration of DCs to the draining lymph nodes and attenuated generation of inflammatory Th1 and Th17 cells that resulted in alleviation of fulminant hepatitis and rheumatoid arthritis. MSCs, in IL‐1Ra‐dependent manner, reduced liver fibrosis by suppressing production of Type I collagen in hepatic stellate cells. IL‐1Ra was, at least partially, responsible for enhanced proliferation of hepatocytes and chondrocytes in MSC‐treated animals with partial hepatectomy and osteoarthritis. Despite of these beneficial effects, IL‐1Ra‐dependent inhibition of IL‐1α/IL‐1β‐signaling significantly increased risk of infections. Therefore, future experimental and clinical studies should delineate potential side effects of MSC‐derived IL‐1Ra before IL‐1Ra‐overexpressing MSCs could be used as a potentially new therapeutic agent for the treatment of acute and chronic inflammatory diseases.

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Focus on Molecules: Interleukin-1: A master regulator of the corneal response to injury

Cited by 43 publications

References 3 publications

Examination of Kynurenine Toxicity on Corneal and Conjunctival Epithelium: In vitro and in vivo Studies

Examination of Kynurenine Toxicity on Corneal and Conjunctival Epithelium: In vitro and in vivo Studies

Corneal myofibroblast viability: Opposing effects of IL-1 and TGF β1

The role of Interleukin 1 receptor antagonist in mesenchymal stem cell‐based tissue repair and regeneration

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