Bromodomain and Extraterminal (BET) Protein Inhibition Restores Redox Balance and Inhibits Myofibroblast Activation
Effect of JQ1 on Antioxidant Response Element- (ARE-) dependent transcription and Nrf2 and Keap1 mRNA expression. (a) Non-ILD control fibroblasts were cotransfected for 48 hours with an inducible ARE-responsive Firefly-luciferase reporter construct and a Renilla-luciferase reference construct. Cells were serum-starved for 24 h and pretreated with 500 nM JQ1(+) or JQ1(-) for 2 h and then stimulated with TGF-β1 (1ng/ml) for 24 h. Bars represent fold change compared to DMSO control. Data points shown are two independent experiments performed in triplicate in two individual non-ILD control cell lines expressed as mean fold change compared to DMSO (vehicle control). (b) Cells were serum-starved for 24 h and pretreated with 500 nM JQ1(+) or JQ1(-) for 2 h before being stimulated with TGF-β1 (1ng/ml) for 24 h. NRF2 and KEAP1 mRNA levels were determined by RT-qPCR. Data are expressed as fold change compared to the JQ1- control. Bars represent mean ± SD of independent experiments in three individual non-ILD control lines. p<0.05 and p<0.01.
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