Purpose
To investigate whether dexamethasone modifies the effect of mitomycin C (MMC) in human Tenon’s capsule fibroblasts (HTFs) and to explore its molecular mechanism.
Methods
HTFs were treated with MMC for 5 minutes and incubated in DMEM with 10 μM dexamethasone (DEX). Viability of the treated HTFs was analyzed by WST-1 assay. The amount of IL-8 section in untreated, MMC-treated, or peroxisome proliferator-activated receptor gamma (PPARγ)-silenced HTFs was determined by enzyme-linked immunosorbent assay. Expression of PPARγ and the apoptotic proteins was examined by immunoblotting.
Results
Recombinant IL-8 noticeably suppressed HTF cell proliferation in a dose-dependent manner. MMC treatment significantly upregulated IL-8 secretion and inhibited cell proliferation in HTFs. Both effects were reversed by DEX incubation. DEX upregulated PPARγ and Bcl-xL in untreated HTFs and MMC-treated HTFs at 1 day and 2 days of incubation, respectively. PPARγ silencing reduced Bcl-xL expression and enhanced IL-8 secretion. However, MMC treatment and/or DEX incubation did not alter the expression of two apoptotic indicators, PARP-1 and pro-caspase-3.
Conclusions
DEX reversed the MMC-inhibited HTF cell proliferation and diminished the MMC-upregulated IL-8 secretion via upregulating the PPARγ expression (Figure 1).
Keywords: 449 cell survival •
490 cytokines/chemokines •
503 drug toxicity/drug effects