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Experimental eye research

Dexamethasone modifies mitomycin C-triggered interleukin-8 secretion in isolated human Tenon's capsule fibroblasts.


PMID 24858696

Abstract

Intraoperative mitomycin C (MMC) is widely used to prevent pterygium recurrence and glaucoma filtering bleb failure, but it has been shown to induce corneal inflammation and cell death. Postoperative dexamethasone (DEX) is advocated to reduce MMC-related inflammation and cell death in corneal fibroblasts. Nevertheless, its long-term regulation mechanism in Tenon's capsule remains to be explored. The purpose of this study was to investigate how DEX modifies MMC's effects in human Tenon's capsule fibroblasts (HTFs). HTFs isolated from the pterygium surgical patients (nxa0=xa06) were treated with MMC at 0, 0.1, 0.2, and 0.4xa0mg/ml for 5xa0min and incubated in DEX at 10xa0μM for 0, 1, 2, and 3 days. Recombinant interleukin-8 (IL-8) was used to verify the effect of MMC-related IL-8 secretion. Cell proliferation of all the treated cells was analyzed by WST-1 assay. The amount of IL-8 secretion in HTFs was determined by enzyme-linked immunosorbent assay. Immunoblotting assay was used to analyze the expression of peroxisome-proliferator-activated receptor gamma (PPARγ) and B-cell lymphoma-extra large (Bcl-xL). Our results revealed that MMC significantly reduced the HTF cell proliferation rate. Additionally, MMC significantly upregulated IL-8 secretion in HTFs concentration-dependently. At 3 days post treatment (dpt), 5-min exposures to 0.1, 0.2, and 0.4xa0mg/ml MMC resulted in 1.4-fold (pxa0=xa00.012), 1.6-fold (pxa0=xa00.012), and 2.5-fold (pxa0=xa00.001) increases of IL-8 secretion. In contrast, DEX reversed the MMC-retarded cell proliferation rate (pxa0=xa00.036) and repressed MMC-related IL-8 secretion by 33.5% at 3xa0dpt (pxa0=xa00.003). Addition of recombinant IL-8 noticeably suppressed HTF cell proliferation in a concentration-dependent manner. DEX stimulated upregulation of both PPARγ and Bcl-xL at 1xa0dpt in normal HTFs and at 2xa0dpt in MMC-treated HTFs. PPARγ silencing reduced expression of PPARγ and Bcl-xL, but enhanced IL-8 secretion (pxa0

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Y0000378 Mitomycin, European Pharmacopoeia (EP) Reference Standard
C15H18N4O5