Effects of Interleukin-6 on posterior capsular opacification

Ma, Bo; Yang, Lan; Jing, Ruihua; Liu, Jie; Quan, Yumeng; Hui, Qiaoyan; Li, Jingming; Li, Qin; Pei, Cheng

doi:10.1016/j.exer.2018.03.013

Cited by 25 publications

(23 citation statements)

References 34 publications

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“…TGF‐β was considered a key member in the development of fibrosis. Our previous and several other studies found that IL‐1, IL‐6 and IL‐17A could enhance the effects of TGF‐β on fibrosis (Fabre, Kared, Friedman, & Shoukry, ; Ma, Yang, et al., ; Qian et al., ; Van Den Akker et al., ). A previous study showed anti‐VEGF could reduce TGF‐β1 expression but not cytokines in the aqueous humor of nAMD patients (Rezar‐Dreindl et al., ).…”

Section: Discussionmentioning

confidence: 79%

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Interleukin‐2 induces extracellular matrix synthesis and TGF‐β2 expression in retinal pigment epithelial cells

Jing

Wen

et al. 2019

Dev Growth Differ

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Macular fibrosis is a vital obstacle of vision acuity improvement of age‐related macular degeneration patients. This study was to investigate the effects of interleukin 2 (IL‐2) on epithelial‐mesenchymal transition (EMT), extracellular matrix (ECM) synthesis and transforming growth factor β2 (TGF‐β2) expression in retinal pigment epithelial (RPE) cells. 10 μg/L IL‐2 was used to induce fibrosis in RPE cells for various times. Western blot was used to detect the EMT marker α‐smooth muscle actin (α‐SMA), ECM markers fibronectin (Fn) and type 1 collagen (COL‐1), TGF‐β2, and the activation of the JAK/STAT3 and NF‐κB signaling pathway. Furthermore, JAK/STAT3 and NF‐κB signaling pathways were specifically blocked by WP1066 or BAY11‐7082, respectively, and the expression of α‐SMA, COL‐1, Fn and TGF‐β2 protein were detected. Wound healing and Transwell assays were used to measure cell migration ability of IL‐2 with or without WP1066 or BAY11‐7082. After induction of IL‐2, the expressions of Fn, COL‐1, TGF‐β2 protein were significantly increased, and this effect was correlated with IL‐2 treatment duration, while α‐SMA protein expression did not change significantly. Both WP1066 and BAY11‐7082 could effectively downregulate the expression of Fn, COL‐1 and TGF‐β2 induced by IL‐2. What's more, both NF‐κB and JAK/STAT3 inhibitors could suppress the activation of the other signaling pathway. Additionally, JAK/STAT3 inhibitor WP1066 and NF‐κB inhibitor BAY 11‐7082 could obviously decrease RPE cells migration capability induced by IL‐2. IL‐2 promotes cell migration, ECM synthesis and TGF‐β2 expression in RPE cells via JAK/STAT3 and NF‐κB signaling pathways, which may play an important role in proliferative vitreoretinopathy.

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Section: Discussionmentioning

confidence: 79%

“…Western blot was performed as described in our previous study (Ma, Yang, et al., ). Briefly, RPE cell lysis was loaded at a concentration of 20 μg per well to separate in SDS‐PAGE and transferred to polyvinylidene difluoride membranes (Bio‐Rad).…”

Section: Methodsmentioning

confidence: 99%

Interleukin‐2 induces extracellular matrix synthesis and TGF‐β2 expression in retinal pigment epithelial cells

Jing

Wen

et al. 2019

Dev Growth Differ

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“…Next, we induced EMT by exposing imLECs to TGFβ2. We chose to treat cells with TGFβ2 as it has been shown to be present in the aqueous humor 18 , it is increased in the aqueous humor following lens injury and inflammation 19, 20 , and it has been shown to be more potent than TGFβ1 in enhancing EMT 21 . Exposure of imLECs to 5ng/mL TGFβ2 downregulated Tpm 1.9 and Tpm1.13 mRNA levels, upregulated Tpm1.7, 2.1, 3.1, and 4.2 mRNA levels, but did not affect Tpm1.5 and Tpm3.5 mRNA levels (Figure 1A and 1B).…”

Section: Resultsmentioning

confidence: 99%

TPM3.1 association with actin stress fibers is required for lens epithelial to mesenchymal transition

Parreno

Amadeo

Kwon

et al. 2019

Preprint

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PurposeEpithelial to mesenchymal transition (EMT) is a cause of anterior and posterior subcapsular cataracts. Central to EMT is the formation of actin stress fibers. Targeting specific, stress fiber associated tropomyosin in epithelial cells may be a means to prevent stress fiber formation and repress lens EMT.MethodsWe identified Tpm isoforms in mouse immortalized lens epithelial cells and isolated whole lenses by semi-quantitative PCR followed Sanger sequencing. We focused on the role of one particular tropomyosin isoform, Tpm3.1, in EMT. To stimulate EMT, we cultured cells or native lenses in TGFβ2. To test the function of Tpm3.1, we exposed cells or whole lenses to a Tpm3.1-specific chemical inhibitor, TR100, as well as investigated lenses from Tpm3.1 knockout mice. We examined stress fiber formation by confocal microscopy and assessed EMT progression by αsma mRNA (qPCR) and protein (WES immunoassay) analysis.ResultsLens epithelial cells express eight tropomyosin isoforms. Cell culture studies showed that TGFβ2 treatment results in an upregulation of Tpm3.1, which associates with actin in stress fibers. TR100 prevents stress fiber formation and reduces αsma in TGFβ2 treated cells. We confirmed the role of Tpm3.1 in lens epithelial cells in the native lens ex vivo. Culture of whole lenses in the presence of TGFβ2 results in stress fiber formation at the basal regions of epithelial cells. Knockout of Tpm3.1 or treatment of lenses with TR100 prevents basal stress fiber formation and reduces epithelial αsma levels.ConclusionTargeting specific stress fiber associated tropomyosin isoform, Tpm3.1, is a means to represses lens EMT.

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“…Daily drug delivery was performed by subconjunctival injection of 10 µl dimethyl sulfoxide (DMSO) in the control group and 10 µl 1,2,4,5-tetraaminobenzene tetrahydrochloride (10 µM) in the treatment group for 60 days. Anterior chamber inflammatory reaction grading was conducted as previously described (27). PCO development grading was performed by slit lamp microscopy (clinical scoring was based on the combination of the area and severity of the opacity (28) and evaluation via EPCO2000 posterior capsule opacification software (http://www.epco2000.de/) (27).…”

Section: Methodsmentioning

confidence: 99%

“…Anterior chamber inflammatory reaction grading was conducted as previously described (27). PCO development grading was performed by slit lamp microscopy (clinical scoring was based on the combination of the area and severity of the opacity (28) and evaluation via EPCO2000 posterior capsule opacification software (http://www.epco2000.de/) (27). Images were captured using retroillumination.…”

Section: Methodsmentioning

confidence: 99%

The role of focal adhesion kinase in transforming growth factor-β2 induced migration of human lens epithelial cells

Liu

et al. 2018

Int J Mol Med

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The migration of lens epithelial cells towards the posterior capsule is a key event in the development of posterior capsule opacification (PCO). Accumulating evidence has described crosstalk between growth factors and adhesive signaling pathways in wound healing and cell migration. The aim of the present study was to elucidate an aberrant transforming growth factor (TGF)-β2 signaling pathway that regulated the migration of lens epithelial cells in the pathological context of PCO. The expression of fibronectin, focal adhesion kinase (FAK) and phosphorylated (p)-FAK in HLE-B3 cells following TGF-β2 treatment was determined by western blot analysis and the expression of integrin α5β1 was detected by flow cytometry. Cell migration capacity was measured by wound healing and Transwell assays in the presence of 1,2,4,5-tetraaminobenzene tetrahydrochloride, a selective FAK inhibitor, fibronectin small interfering RNA interference, arginylglycylaspartic acid peptides or α5β1-integrin neutralizing antibodies. The 1,2,4,5-tetraaminobenzene tetrahydrochloride was administered daily to 16 rabbits following cataract surgery. Fibronectin and TGF-β expression were increased in the PCO group, demonstrated by immunofluorescence assays. PCO grading was conducted by slit-lamp biomicroscopy and evaluation of posterior capsule opacification software. It was observed that TGF-β2 promoted HLE-B3 cell migration and upregulated fibronectin expression, which was followed by an increased phosphorylation of FAK. In addition, TGF-β2 treatment and fibronectin surface coating significantly increased cell migration and FAK activation, which was inhibited by disrupting fibronectin-integrin α5β1 interaction with the arginylglycylaspartic acid peptide, α5β1-integrin neutralizing antibody or fibronectin depletion. Finally, suppression of FAK signaling by its inhibitor significantly decreased cell migration in vitro and attenuated PCO development in vivo. In summary, TGF-β2 was indicated to promote the migration of lens epithelial cells through the TGF-β2/fibronectin/integrin/FAK axis. Inhibition of FAK activity decreased TGF-β2-mediated cell migration in vitro and improved the symptoms of PCO in a rabbit model.

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Effects of Interleukin-6 on posterior capsular opacification

Cited by 25 publications

References 34 publications

Interleukin‐2 induces extracellular matrix synthesis and TGF‐β2 expression in retinal pigment epithelial cells

Interleukin‐2 induces extracellular matrix synthesis and TGF‐β2 expression in retinal pigment epithelial cells

TPM3.1 association with actin stress fibers is required for lens epithelial to mesenchymal transition

The role of focal adhesion kinase in transforming growth factor-β2 induced migration of human lens epithelial cells

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