Effect of bevacizumab on the expression of fibrosis-related inflammatory mediators in ARPE-19 cells

• Main Authors: San-Jun Chu, Zhao-Hua Zhang, Min Wang, Hai-Feng Xu
• Format: Article
• Language: English
• Published: Press of International Journal of Ophthalmology (IJO PRESS) 2017-03-01
• Series: International Journal of Ophthalmology
• Subjects: bevacizumab; fibrosis; human retinal pigment epithelial cells; inflammatory mediators
• Online Access: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360770/

AIM: To investigate the effect of anti-vascular epithelial growth factor (VEGF) agents on the expression of fibrosis-related inflammatory mediators under normoxic and hypoxic conditions, and to further clarify the mechanism underlying fibrosis after anti-VEGF therapy. METHODS: Human retinal pigment epithelial (RPE) cells were incubated under normoxic and hypoxic conditions. For hypoxia treatment, CoCl2 at 200 μmol/L was added to the media. ARPE-19 cells were treated as following: 1) control group: no treatment; 2) bevacizumab group: bevacizumab at 0.25 mg/mL was added to the media; 3) hypoxia group: CoCl2 at 200 μmol/L was added to the media; 4) hypoxia+bevacizumab group: CoCl2 at 200 μmol/L and bevacizumab at 0.25 mg/mL were added to the media. The expression of interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF)-α were evaluated using real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) at 6, 12, 24 and 48h. RESULTS: Both mRNA and protein levels of IL-1β, IL-6 and IL-8 were statistically significantly higher in the bevacizumab group than in the control group at each time point, and TNF-α gene and protein expression was only significantly higher only at 24 and 48h (P<0.05). Under hypoxic conditions, bevacizumab significantly increased the expression of IL-1β, IL-6, IL-8 and TNF-α at 6, 12, 24 and 48h (P<0.05). IL-1β, IL-8 and TNF-α peaked at 24h and IL-6 peaked at 12h after the bevacizumab treatment under both normoxic and hypoxic conditions. CONCLUSION: Treatment of ARPE-19 cells with bevacizumab can significantly increase the expression of fibrosis-related inflammatory mediators under both normoxic and hypoxic conditions. Inflammatory factors might be involved in the process of fibrosis after anti-VEGF therapy, and the up-regulation of inflammatory factors induced by anti-VEGF drugs might promote the fibrosis process.