Allyl Isothiocyanate Increases MRP1 Function and Expression in a Human Bronchial Epithelial Cell Line

Abstract EN

Multidrug resistance-associated protein 1 (MRP1), a member of the ATP-bindingcassette (ABC) superfamily of transporters, plays an important role in normal lungphysiology by protecting cells against oxidative stress and toxic xenobiotics.

The presentstudy investigates the effects of allyl isothiocyanate (AITC) on MRP1 mRNA and MRP1protein expression and transporter activity in the immortalised human bronchial epithelialcell line 16HBE14o-.

MRP1 mRNA and MRP1 protein expression in 16HBE14o- cellsthat were treated with allyl isothiocyanate were analysed by real-time PCR assay andWestern blotting.

The transport of carboxyfluorescein, a known MRP1 substrate, wasmeasured by functional flow cytometry to evaluate MRP1 activity.

Treatment with AITCat concentrations of 5–40 μM increased MRP1 protein levels in aconcentration-dependent manner.

AITC treatments at concentrations of 1–40 μM causedconcentration-dependent increases in MRP1 mRNA levels that were up to seven timesgreater than the levels found in control cells.

Finally, AITC treatment at concentrations of5–40 μM significantly increased MRP1-dependent efflux in 16HBE14o- cells.

Theseresults suggest that AITC can increase the expression and activity of MRP1 in16HBE14o- cells in a concentration-dependent manner.

The upregulation of MRP1activity and expression by AITC could produce therapeutic effects in the treatment oflung disease.