Dexamethasone Inhibition of IL-1–Induced Collagen Degradation by Corneal Fibroblasts in Three-Dimensional Culture

Lü, Ying; Fukuda, Ken; Liu, Yang; Kumagai, Naoya; Nishida, Teruo

doi:10.1167/iovs.04-0051

Cited by 46 publications

(49 citation statements)

References 29 publications

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“…We have previously shown that dexamethasone and female sex hormones as well as ATRA also inhibit collagen degradation by corneal fibroblasts likely through suppression of MMP expression. 14,16,17,21 These data thus suggest that RAR-c signaling modulates the expression of MMPs in corneal fibroblasts and thereby contributes to the regulation of collagen remodeling in the corneal stroma both under physiological conditions and during the development of pathologic conditions such as corneal infection, scar formation, and inflammation. Indeed, we have recently found that topical application of ATRA ameliorates corneal ulceration induced by injection of bacterial lipopolysaccharide into the corneal stroma of rabbits.…”

Section: Discussionmentioning

confidence: 84%

“…We have previously shown that the amounts of pro or active forms of MMP-1, MMP-2, MMP-3, and MMP-9 in such culture supernatants are increased by exposure of the cells to IL-1b 14 and that these effects are inhibited by ATRA. 17 Immunoblot analysis and gelatin zymography revealed that the amount of ProMMP-1, active MMP-1, ProMMP-2, active MMP-2, ProMMP-3, active MMP-3, ProMMP-9, and active MMP-9 in the supernatants from cultured cells were increased by IL-1b.…”

Section: Effects Of R667 On Mmp Expressionmentioning

confidence: 99%

“…13 Collagen degradation by corneal fibroblasts in three-dimensional culture has been studied as a means to characterize the remodeling of collagen fibrils in the corneal stroma. [14][15][16] We have recently shown that ATRA inhibits IL-1b-induced collagen degradation by corneal fibroblasts in a manner likely dependent on attenuation of nuclear factor (NF)-jB signaling and MMP production. 17 We now examined the effects RAR agonists including those selective for RAR-a, RAR-b, and RAR-c on IL-1b-induced collagen degradation by rabbit corneal fibroblasts as well as on the release of MMPs by, and the activity of signaling pathways in, these cells.…”

mentioning

confidence: 99%

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Suppression by an RAR-γ Agonist of Collagen Degradation Mediated by Corneal Fibroblasts

Kimura

Zhou

Orita

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To examine the role of retinoic acid receptor (RAR) isoforms in interleukin-1b (IL1b)-induced collagen degradation by corneal fibroblasts.METHODS. Primary rabbit corneal fibroblasts embedded in a three-dimensional collagen gel were incubated with or without all-trans retinoic acid (ATRA), the RAR-a agonist Am580, the RAR-b agonist AC55649, or the RAR-c agonist R667. Collagen degradation was determined by measurement of hydroxyproline produced in acid hydrolysates of culture supernatants. Matrix metalloproteinase (MMP) expression was evaluated by immunoblot analysis and gelatin zymography. The phosphorylation of mitogen-activated protein kinases (MAPKs) and the endogenous nuclear factor (NF)-jB inhibitor IjB-a was examined by immunoblot analysis. Cell proliferation was measured with a bromodeoxyuridine incorporation assay, and cell viability was determined by measurement of the release of lactate dehydrogenase. RESULTS.Interleukin-1b-induced collagen degradation by corneal fibroblasts was inhibited by ATRA, Am580, and R667 in a concentration-dependent manner but was unaffected by AC55649, with the inhibitory effects of ATRA and R667 being markedly greater than that of Am580. The IL-1b-induced production of MMP-1, MMP-2, MMP-3, and MMP-9 by corneal fibroblasts was also inhibited by R667 in a concentration-dependent manner. R667 inhibited the IL-1b-induced phosphorylation of IjB-a but not that of MAPKs. R667 had no effect on the proliferation or viability of corneal fibroblasts.CONCLUSIONS. The RAR-c agonist R667 suppressed MMP production and thereby inhibited collagen degradation by corneal fibroblasts exposed to the proinflammatory cytokine IL-1b. These effects of R667 may be mediated by the NF-jB signaling pathway.

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Section: Discussionmentioning

confidence: 84%

Section: Effects Of R667 On Mmp Expressionmentioning

confidence: 99%

mentioning

confidence: 99%

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Suppression by an RAR-γ Agonist of Collagen Degradation Mediated by Corneal Fibroblasts

Kimura

Zhou

Orita

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…38 After corneal injury, IL-1 protein is detectable in corneal fibroblasts. IL-1 up-regulates the expression of various cytokines or enzymes by corneal fibroblasts, 8,22,39 and it also contributes to wound healing. In our model, IL-1␤ binds to the IL-1 receptor on corneal fibroblasts, up-regulates various angiogenesis-related factors, and induces corneal neovascularization.…”

Section: Discussionmentioning

confidence: 99%

“…20 NF-B plays an important role in IL-1␤-related inflammatory diseases, including various corneal diseases. 21,22 Blockade of NF-B reduces corneal epithelial defects during healing in a model of corneal injury. 21 However, it is unknown whether dexamethasone has an impact on IL-1␤-dependent angiogenesis.…”

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confidence: 99%

Dexamethasone Inhibits Interleukin-1β-Induced Corneal Neovascularization

Nakao

Hata

Matsuda

et al. 2007

The American Journal of Pathology

104

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Dexamethasone, a synthetic corticosteroid, is widely used as a potent anti-inflammatory drug in various diseases including corneal angiogenesis. However, dexamethasone's impact on interleukin (IL)-1␤-dependent inflammatory angiogenesis is unknown. Here, we show that dexamethasone inhibits IL-1␤-induced neovascularization and the expression of the angiogenesis-related factors, vascular endothelial growth factor-A, KC, and prostaglandin E 2 in the mouse cornea 2 days after IL-1␤ implantation. IL-1␤ caused IB-␣ phosphorylation in corneal stromal cells but not in infiltrated CD11b

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Maturational changes in laminin, fibronectin, collagen IV, and perlecan in germinal matrix, cortex, and white matter and effect of betamethasone

Sado

et al. 2008

J of Neuroscience Research

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Germinal matrix is selectively vulnerable to hemorrhage in premature infants, and use of prenatal betamethasone is associated with a lower occurrence of germinal matrix hemorrhage. Because the major components of extracellular matrix of the cerebral vasculature-laminin, fibronectin, collagen IV, and perlecan-provide structural stability to blood vessels, we examined whether the expression of these molecules was decreased in the germinal matrix and affected by betamethasone. In both human fetuses and premature infants, fibronectin was significantly lower in the germinal matrix than in the cortical mantle or white matter anlagen. Conversely, laminin alpha1 gene expression was greater in the human germinal matrix compared with the cortical mantle or white matter. Expression of alpha1- and alpha2(IV) collagen chains increased with advancing gestational age. Low-dose prenatal betamethasone treatment enhanced fibronectin level by 1.5-2-fold whereas a high dose reduced fibronectin expression by 2-fold in rabbit pups. Because fibronectin provides structural stability to the blood vessels, its reduced expression in the germinal matrix may contribute to the fragility of germinal matrix vasculature and the propensity to hemorrhage in premature neonates.

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Dexamethasone Inhibition of IL-1–Induced Collagen Degradation by Corneal Fibroblasts in Three-Dimensional Culture

Abstract: Dexamethasone exerted multiple effects on the MMP-TIMP system in corneal fibroblasts and thereby inhibited IL-1beta-induced collagen degradation by these cells. Inhibition of the IL-1beta-induced activation of ERK and JNK may contribute to these effects of dexamethasone.

Cited by 46 publications

References 29 publications

Suppression by an RAR-γ Agonist of Collagen Degradation Mediated by Corneal Fibroblasts

Suppression by an RAR-γ Agonist of Collagen Degradation Mediated by Corneal Fibroblasts

Dexamethasone Inhibits Interleukin-1β-Induced Corneal Neovascularization

Maturational changes in laminin, fibronectin, collagen IV, and perlecan in germinal matrix, cortex, and white matter and effect of betamethasone

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