The effect of clonidine on VEGF expression in human retinal pigment epithelial cells (ARPE-19)

Watanabe, Kazuhiko; Zhang, Xueyun; Kitagawa, Kiyotaka; Yunoki, Tatsuya; Hayashi, Atsushi

doi:10.1007/s00417-008-0990-5

Cited by 11 publications

(6 citation statements)

References 34 publications

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“…The concentrations of these substances positively correlated with the anticancer activity demonstrated by the strains. Interestingly, several reports have proven that oleic acid, oleanolic acid, yohimbine and cytidine possess anticancer activity by the suppressing tumour metastasis [ 35 – 38 ]. Furthermore, natural products containing these compounds have been reported to inhibit the expression of VEGF.…”

Section: Discussionmentioning

confidence: 99%

Metabolite secretions of Lactobacillus plantarum YYC-3 may inhibit colon cancer cell metastasis by suppressing the VEGF-MMP2/9 signaling pathway

Yue

Yang

et al. 2020

Microb Cell Fact

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Background Colorectal cancer (CRC) is a major clinical challenge, and the gut microbiome plays important roles in the occurrence and metastasis of CRC. Lactobacillus and their metabolites are thought to be able to suppress the growth of CRC cells. However, the antimetastatic mechanism of Lactobacillus or their metabolites toward CRC cells is not clear. Therefore, the aim of this study was to assess the inhibitory mechanism of cell-free supernatants (CFSs) of L. rhamnosus GG, L. casei M3, and L. plantarum YYC-3 on metastasis of CRC cells. Results YYC-3 CFS showed the highest inhibitory effect on CRC cell growth, invasion and migration, and inhibited MMP2, MMP9, and VEGFA gene and protein expression, and protein secretion. Furthermore, it suppressed the activities of MMPs by gelatin zymography. Moreover, the effective compounds in these CFSs were analyzed by Q Exactive Focus liquid chromatography–mass spectrometry. Conclusions Our results showed that metabolite secretions of YYC-3 may inhibited cell metastasis by downregulating the VEGF/MMPs signaling pathway. These data suggest that treatment of CRC cells with metabolites from L. plantarum YYC-3 may reduce colon cancer metastasis.

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Section: Discussionmentioning

confidence: 99%

Metabolite secretions of Lactobacillus plantarum YYC-3 may inhibit colon cancer cell metastasis by suppressing the VEGF-MMP2/9 signaling pathway

Yue

Yang

et al. 2020

Microb Cell Fact

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“…28 It was previously reported that ARPE19 cells could produce inflammatory cytokines under the stimulation of TNFa or IL-1b, through ERK1/2 and JNK pathways, 54,55 which indicate possible methods to control inflammatory retinal diseases by inhibiting these inflammatory factors and pathways. 55,56 Moreover, previous study indicated that these cytokines were related to Th1 differentiation. 36 We found that neutralization of IL-1b inhibited A2E-laden RPE cell function on Th1-cell differentiation.…”

Section: Discussionmentioning

confidence: 99%

A2E Suppresses Regulatory Function of RPE Cells in Th1 Cell Differentiation Via Production of IL-1β and Inhibition of PGE2

Shi

Qiu

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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Citation: Shi Q, Wang Q, Li J, et al. A2E suppresses regulatory function of RPE cells in Th1 cell differentiation via production of IL-1b and inhibition of PGE2. Invest Ophthalmol Vis Sci. 2015;56:7728-7738. DOI:10.1167/ iovs.15-17677 PURPOSE. Inflammatory status of RPE cells induced by A2E is essential in the development of AMD. Recent research indicated T-cell immunity was involved in the pathological progression of AMD. This study was designed to investigate how A2E suppresses immunoregulatory function of RPE cells in T-cell immunity in vitro. METHODS.Mouse RPE cells or human ARPE19 cells were stimulated with A2E, and co-cultured with naïve T cells under Th1, Th2, Th17, and regulatory T cell (Treg) polarization conditions. The intracellular cytokines or transcript factors of the induced T-cells subset were detected with flow cytometer and qRT-PCR. The ROS levels were detected, and the factors and possible pathways involved in the A2E-laden RPE cells were analyzed through neutralization antibody of IL-1b and inhibitors of related pathways. RESULTS.The A2E reduced regulatory function of RPE cells in Treg differentiation. The A2E-laden RPE cells promoted polarization of Th1 cells in vitro, but not Th2 or Th17 differentiation. The A2E induced RPE cells to release inflammatory cytokines and ROS, but PGE2 production was inhibited. Through neutralization of IL-1b or inhibition of COX2-PGE2 pathways, A2E-laden RPE cells expressed reduced effect in inducing Th1 cells. CONCLUSIONS.The A2E inhibited regulatory function of RPE cells in suppressing Th1 cell immunity in vitro through production of IL-1b and inhibition of PGE2. Our data indicate that A2E could suppress immunoregulatory function of RPE cells and adaptive immunity might play a role in the immune pathogenesis of AMD.

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“…1 ), which is likely caused by both the CRVO-induced tissue hypoxia and retinal inflammation. It has been shown that inflammatory factors such as IL-1 ␤ cause an upregulation of Vegfa in retinal cells [17,18] . The decrease in the expression of Vegfa after 3 days of CRVO might be related to the upregulation of Pedf observed for this time period ( fig.…”

Section: Discussionmentioning

confidence: 99%

Effect of Intravitreal Anti-Vascular Endothelial Growth Factor Treatment on the Retinal Gene Expression in Acute Experimental Central Retinal Vein Occlusion

et al. 2011

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Purpose: To determine the effect of intravitreal bevacizumab and anti-vascular endothelial growth factor (VEGF) antibodies on the gene expression in the neural retina in a rat model of central retinal vein occlusion (CRVO). Methods: The CRVO was induced by laser photocoagulation of all retinal veins. The animals were divided into 3 groups (in each, n = 16): group CRVO only without any further treatment, group CRVO with bevacizumab, and group CRVO with anti-VEGF antibodies. The intravitreal injection of bevacizumab or anti-VEGF antibodies was performed 15 min after CRVO induction. The left eyes in all animals served as untreated controls. The expression of factors which influence the development of vascular edema (VEGF-A, pigment epithelium-derived factor, PEDF), of channels implicated in retinal osmohomeostasis (Kir4.1, AQP4, AQP1) and of the proinflammatory cytokines interleukin (IL)-1β and IL-6 was determined by using real-time RT-PCR after 1 and 3 days of CRVO. Results: CRVO induced a rapid transient upregulation of Vegfa after 1 day, and a delayed upregulation of Pedf after 3 days of CRVO. The expression levels of Kir4.1, Aqp4 and Aqp1 were strongly decreased, and the levels of Il1β and Il6 were strikingly increased after CRVO. Intravitreal bevacizumab and anti-VEGF antibodies fully prevented the upregulation of Vegfa after 1 day, and the upregulation of Pedf after 3 days of CRVO, and decreased the upregulation of Il1β after 1 day of CRVO. Anti-VEGF treatment had no effect on the expression levels of Kir4.1, Aqp4, Aqp1, and Il6. Conclusions: It is suggested that the inhibitory effect on the upregulation of Vegfa and Il1β contributes to the edema-resolving effect of anti-VEGF treatment.

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The effect of clonidine on VEGF expression in human retinal pigment epithelial cells (ARPE-19)

Abstract: The effect of clonidine on the expression of VEGF may be via suppression of the p38MAPK and MEK1/2 signal transduction pathways activated with IL-1beta.

Cited by 11 publications

References 34 publications

Metabolite secretions of Lactobacillus plantarum YYC-3 may inhibit colon cancer cell metastasis by suppressing the VEGF-MMP2/9 signaling pathway

Metabolite secretions of Lactobacillus plantarum YYC-3 may inhibit colon cancer cell metastasis by suppressing the VEGF-MMP2/9 signaling pathway

A2E Suppresses Regulatory Function of RPE Cells in Th1 Cell Differentiation Via Production of IL-1β and Inhibition of PGE2

Effect of Intravitreal Anti-Vascular Endothelial Growth Factor Treatment on the Retinal Gene Expression in Acute Experimental Central Retinal Vein Occlusion

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