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


OBJECTIVE
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.


METHODS
We administered the recombinant adenovirus Ax1CAlacZ, which encodes Escherichia coli beta-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 beta-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 beta-galactosidase protein persisted in the dexamethasone-treated mice at Days 7 and 14 but had diminished almost to nothing in the control group.
Kumahara
Keiichiro
K
Department of Otorhinolaryngology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Nagata
Hiroshi
H
Watanabe
Ken
K
Shimizu
Norio
N
Arimoto
Yukiko
Y
Isoyama
Kyoko
K
Okamoto
Yoshitaka
Y
Shirasawa
Hiroshi
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009297:Nasal Mucosa / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D012016:Reference Values; D012680:Sensitivity and Specificity
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D003907:Dexamethasone