Non-polarized secretion of mouse interferon-beta from gene-transferred human intestinal Caco-2 cells.
OBJECTIVE
The intestinal epithelium is considered to be a feasible target for somatic gene therapy. To this end, Caco-2 cells derived from human colon carcinoma were transfected with a mouse interferon-beta (IFN-beta) expression vector and several stable sublines were established; this hetero-specific cytokine allows unexpected cellular effects to be avoided. Using the highest mouse IFN-beta-producing sublines, the mode of IFN secretion was examined.


METHODS
The secretion polarity of mouse IFN-beta in its gene-transduced Caco-2 sublines was studied in a bicameral culture system in which the chambers were separated by microporous filters.


RESULTS
Mouse IFN-beta was secreted to the same extent from both apical and basolateral surfaces of the transduced cells regardless of cell aging.


CONCLUSIONS
These results suggest that in the intestinal epithelium exogenous gene products such as IFNs can be delivered to both the luminal and blood sides in vivo. Thus, the intestinal epithelium may be suitable for systemic and local delivery of therapeutic proteins by gene transfer.
Kawabata
K
K
Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Kondo
M
M
Watanabe
Y
Y
Takakura
Y
Y
Hashida
M
M
D000818:Animals; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D018076:DNA, Complementary; D018014:Gene Transfer Techniques; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism* / Q000493:pharmacokinetics; D051379:Mice; D016133:Polymerase Chain Reaction
D018076:DNA, Complementary; D016899:Interferon-beta