Down-regulated expression of CC chemokine receptor 3 ligands in ranibizumab treated light-injured human retinal pigment epithelium cells_Chinese Journal of Ocular Fundus Diseases

Authors：

PanYingzhe ,  XingYiqiao , ChenChangzheng , 黎智 , 王慧 , 李璐 , 苏钰

Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan 430060, China;

Corresponding author：

XingYiqiao, Email: xyqdr07@aliyun.com

Keywords：

Retinal pigment epithelium; Vascular endothelial growth factor A; Receptors; CCR3

DOI：

10.3760/cma.j.issn.1005-1015.2015.01.016

Video：

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Objective To observe the changes of eotaxin-1(CCL11), eotaxin-2(CCL24)and eotaxin-3(CCL26)in ranibizumab treated light-injured human retinal pigment epithelium (RPE) cells ARPE-19 and investigate the effects of vascular endothelial growth factor (VEGF) antagonist to the expressions of eotaxins. Methods Cultured human RPE cells(8th-12th generations)were divided into light-injured group, ranibizumab treated group and normal control group. Cells of the three groups were exposed to the blue light at the intensity of(600±100) Lux for 12 h to establish the light injured model, while cell culture dishes of the normal control group were wrapped with double-layer foil. The cells of ranibizumab treated group were treated with VEGF-A antagonist(ranibizumab)at the final concentration of 0.125 mg/ml for 24 hours directly after the illumination. The mRNA and protein of VEGF-A, eotaxin-1, eotaxin-2, eotaxin-3, NF-κB were determined by Real time-PCR, enzyme-linked immunosorbent assay, Western blot, immunohistochemical staining at 0, 3, 6, 12, 24 hours after light damage. Results The mRNA and protein level of VEGF-A, eotaxin-1, eotaxin-2, eotaxin-3, NF-κB in the light-injuried group increased significantly compared to that in normal control group (P < 0.05). After treating with ranibizumab, the expression of eotaxin-1, eotaxin-2, eotaxin-3, NF-κB were significantly suppressed (P < 0.05). Conclusion The suppression of over-expression of VEGF in human RPE may down-regulate the expression of eotaxins, via the suppression of NF-κB.

Citation： PanYingzhe, XingYiqiao, ChenChangzheng. Down-regulated expression of CC chemokine receptor 3 ligands in ranibizumab treated light-injured human retinal pigment epithelium cells. Chinese Journal of Ocular Fundus Diseases, 2015, 31(1): 62-66. doi: 10.3760/cma.j.issn.1005-1015.2015.01.016 Copy

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11.	Okamoto T, Yamagishi S, Inagaki Y, et al. Angiogenesis induced by advanced glycation end products and its prevention by cerivastatin[J]. FASEB J, 2002, 16(14):1928-1930.
12.	Tabruyn SP, Griffioen AW. A new role of NF-κB in angiogenesis inhibition[J]. Cell Death Differ, 2007, 14(8):1-5.
13.	Poynter ME, Irvin CG, Janssen-Heininger YM. Rapid activation of nuclear factor-kappa B in airway epithelium in a murine model of allergic airway inflammation[J]. Am J Pathol, 2002, 160(4):1325-1334.
14.	Huber MA, Denk A, Peter RU, et al. The IKK-2/Ikappa Balpha/NF-kappa B pathway plays a key role in the regulation of CCR3 and eotaxin-1 in fibroblasts:a critical link to dermatitis in Ikappa Balpha-deficient mice[J]. J Biol Chem, 2002, 277(2):1268-1275.

1. Takeda A, Baffi JZ, Kleinman ME, et al. CCR3 is a target for age-related macular degeneration diagnosis and therapy[J]. Nature, 2009, 460(7252):225-230.
2. Wang H, Wittchen ES, Jiang Y, et al. Upregulation of CCR3 by age-related stresses promotes choroidal endothelial cell migration via VEGF dependent and independent signaling[J]. Invest Ophthalmol Vis Sci, 2011, 52(11):8271-8277.
3. 李菲, 陈长征, 周俊.光损伤人视网膜色素上皮细胞后血管内皮生长因子及其受体的变化[J].中华眼底病杂志, 2012, 28(2):159-162.
4. 李璐, 陈长征, 易佐慧子, 等.光照对人视网膜色素上皮细胞趋化因子受体3配体的影响[J].中华眼底病杂志, 2013, 29(4):416-420.
5. Kernt M, Thiele S, Neubauer AS, et al. Inhibitory activity of ranibizumab, sorafenib, and pazopanib on light-induced overexpression of platelet-derived growth factor and vascular endothelial growth factor A and the vascular endothelial growth factor A receptors 1 and 2 and neuropilin 1 and 2[J]. Retina, 2012, 32(8):1652-1663.
6. Ambati J, Ambati BK, Yoo SH, et al. Age-related macular degeneration:etiology, pathogenesis, and therapeutic strategies[J]. Surv Ophtalmol, 2003, 48(3):257-293.
7. Wu J, Seregard S, Algvere PV. Photochemical damage of the retina[J]. Surv Ophthalmol, 2006, 51(5):461-481.
8. Kernt M, Neubauer AS, Liegl RG, et al. Sorafenib prevents human retinal pigment cells from light-induced overexpression of VEGF, PDGF and PIGF[J]. Br J Ophthalmol, 2010, 94(11):1533-1539.
9. Mizutani T, Ashikari M, Tokoro M, et al. Suppression of laser-induced choroidal neovascularization by a CCR3 antagonist[J]. Invest Ophthalmol Vis Sci, 2013, 54(2):1564-1572.
10. 张蕾, 周占宇, 牛膺筠.核因子-κB与视网膜疾病[J].眼科研究, 2006, 24(2):212-215.
11. Okamoto T, Yamagishi S, Inagaki Y, et al. Angiogenesis induced by advanced glycation end products and its prevention by cerivastatin[J]. FASEB J, 2002, 16(14):1928-1930.
12. Tabruyn SP, Griffioen AW. A new role of NF-κB in angiogenesis inhibition[J]. Cell Death Differ, 2007, 14(8):1-5.
13. Poynter ME, Irvin CG, Janssen-Heininger YM. Rapid activation of nuclear factor-kappa B in airway epithelium in a murine model of allergic airway inflammation[J]. Am J Pathol, 2002, 160(4):1325-1334.
14. Huber MA, Denk A, Peter RU, et al. The IKK-2/Ikappa Balpha/NF-kappa B pathway plays a key role in the regulation of CCR3 and eotaxin-1 in fibroblasts:a critical link to dermatitis in Ikappa Balpha-deficient mice[J]. J Biol Chem, 2002, 277(2):1268-1275.

Chinese Journal of Ocular Fundus Diseases

Down-regulated expression of CC chemokine receptor 3 ligands in ranibizumab treated light-injured human retinal pigment epithelium cells

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