Suppression of inflammation by dexamethasone prolongs adenoviral vector-mediated transgene expression in murine nasal mucosa

Abstract

Conclusion. The results of this study demonstrate that suppression of inflammation by dexamethasone attenuates the host immune response against adenoviral-mediated gene transfection and thereby prolongs transgene expression in murine nasal mucosa. Objectives. Gene transfer using a recombinant adenovirus is a good tool for research and clinical applications, but the immune response to adenoviral vectors can induce inflammation and loss of transgene expression in transfected tissues. In this study we investigated the effects of dexamethasone-induced immunosuppression on adenovirus gene transfer in the nasal mucosa of the mouse. Material and methods. We administered the recombinant adenovirus Ax1CAlacZ, which encodes Escherichia coli β-galactosidase (lacZ gene), to the nasal mucosa of mice treated with or without i.p. dexamethasone and evaluated the expression of the lacZ gene on Days 2, 4, 7, 14 and 28. The nasal mucosa was dissected out, and the mRNA level was measured using a LightCycler. The expression of the exogenous β-galactosidase was detected by means of histochemistry. Results. Dexamethasone treatment significantly increased the mRNA level compared with that in the controls at Days 4, 7 and 14. Histochemistry showed that the expression of β-galactosidase protein persisted in the dexamethasone-treated mice at Days 7 and 14 but had diminished almost to nothing in the control group.

• Gene transfer
• glucocorticoids
• lacZ
• recombinant adenovirus