Skip to main content
Log in

Non-Polarized Secretion of Mouse Interferon-β from Gene-Transferred Human Intestinal Caco-2 Cells

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose. 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-β (IFN-β) expression vector and several stable sublines were established; this hetero-specific cytokine allows unexpected cellular effects to be avoided. Using the highest mouse IFN-β-producing sublines, the mode of IFN secretion was examined.

Methods. The secretion polarity of mouse IFN-β 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-β 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. T. Fujita, M. Nishikawa, C. Tamaki, Y. Takakura, M. Hashida, and H. Sezaki. J. Pharmacol. Exp. Ther. 263:971–978 (1992).

    Google Scholar 

  2. T. Fujita, H. Furitsu, M. Nishikawa, Y. Takakura, H. Sezaki, and M. Hashida. Biochem. Biophys. Res. Commun. 189:191–196 (1992).

    Google Scholar 

  3. M. Pinto, S. Robine-Leon, M. D. Appay, M. Kedinger, N. Triadou, E. Dussaulx, B. Lacroix, P. Simon-Assmann, K. Haffen, J. Fogh, and A. Zweibaum. Biol. Cell 47:323–330 (1983).

    Google Scholar 

  4. J. L. Madara. In: S. G. Schultz, M. Field, R. A. Frizzell, and B. B. Rauner (eds.) Handbook of Physiology: Functional Morphology of Epithelium of the Small Intestine, American Physiological Society, Bethesda, MD, 1991, pp. 83–120.

    Google Scholar 

  5. Y. Higashi, Y. Sokawa, Y. Watanabe, Y. Kawade, S. Ohno, C. Takaoka, and T. Taniguchi. J. Biol. Chem. 258:9522–9529 (1983).

    Google Scholar 

  6. P. Chomczynski and N. Sacchi. Anal. Biochem. 162:156–159 (1987).

    Google Scholar 

  7. Y. Watanabe, K. Kuribayashi, S. Miyatake, K. Nishihara, E. Nakayama, T. Taniyama, and T. Sakata. Proc. Natl. Acad. Sci. USA 86:9456–9460 (1989).

    Google Scholar 

  8. Y. Watanabe and Y. Kawade. In M. J. Clemens, A. G. Morris, and J. M. Gearing (eds.), Lymphokines and Interferons: A Pratical Approach, IRL, Oxford, 1987, pp. 1–14.

    Google Scholar 

  9. Y. Watanabe, M. Taguchi, A. Iwata, Y. Nanba, Y. Kawade, and M. Hanaoka. In E. De Maeyer and H. Schellekens (eds.), The Biology of The Interferon System 1983, Elsevier, Amsterdam, 1983, pp. 143–148.

    Google Scholar 

  10. Y. Kawade and Y. Watanabe. In K. Cantell and H. Schellekens (eds.), The Biology of The Interferon System 1986, Nijhoff, Dordrecht, 1987, pp. 197–201.

    Google Scholar 

  11. G. L. Spitalny and E. A. Havell. J. Exp. Med. 159:1560–1565 (1984).

    Google Scholar 

  12. F. D. Ledley. J. Pediatr. Gastroenterol. Nutr. 14:328–337 (1992).

    Google Scholar 

  13. R. A. Noel, P. Shukla, and S. J. Henning. J. Pediatr. Gastroenterol. Nutr. 19:43–49 (1994).

    Google Scholar 

  14. S. J. Henning. Adv. Drug Delivery. Rev. 17:341–347 (1995).

    Google Scholar 

  15. J. W. Sandberg, C. Lau, M. Jacomino, M. Finegold, and S. J. Henning. Hum. Gene Ther. 5:323–329 (1994).

    Google Scholar 

  16. C. Lau, H. E. Soliano, F. D. Ledley, M. J. Finegold, J. H. Wolfe, E. H. Birkenmeier, and S. J. Henning. Hum. Gene Ther. 6:1145–1151 (1995).

    Google Scholar 

  17. M. J. Rindler and M. G. Traber. J. Cell Biol. 107:471–479 (1988).

    Google Scholar 

  18. M. G. Traber, H. J. Kayden, and M. J. Rindler. J. Lipid Res. 28:1350–1363 (1987).

    Google Scholar 

  19. A. T. Remaley and J. M. Hoeg. J. Lipid Res. 36:407–413 (1995).

    Google Scholar 

  20. G. W. Varilek, G. A. Neil, W. P. Bishop, J. Lin, and N. J. Pantazis. Am. J. Physiol. 269:G445–G452 (1995).

    Google Scholar 

  21. R. Canipari, C. Zurzolo, C. Polistina, C. Carbi, L. Aloj, G. Cali, R. Gentile, and L. Nitsch. Biochim. Biophys. Acta 1175:1–6 (1992).

    Google Scholar 

  22. L. K. Vogel, G. Suske, M. Beato, O. Noren, and H. Sjostrom. FEBS Lett. 330:293–296 (1993).

    Google Scholar 

  23. J. Klumperman, J. A. M. Fransen, T. C. Boekestijn, R. P. J. Oude Elferink, K. Matter, H. P. Hauri, J. M. Tager, and L. A. Ginsel. J. Cell Sci. 100:339–347 (1991).

    Google Scholar 

  24. D. H. Perlmutter, J. D. Daniels, H. S. Auerbach, K. D. Schryver-Kecskemeti, H. S. Winter, and D. H. Alpers. J. Biol. Chem. 264:9485–9490 (1989).

    Google Scholar 

  25. K. L. Soole, J. Hall, M. A. Jepson, G. P. Hazlewood, H. J. Gilbert, and B. H. Hirst. J. Cell Sci. 102:495–504 (1992).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mitsuru Hashida.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kawabata, K., Kondo, M., Watanabe, Y. et al. Non-Polarized Secretion of Mouse Interferon-β from Gene-Transferred Human Intestinal Caco-2 Cells. Pharm Res 14, 483–485 (1997). https://doi.org/10.1023/A:1012151616910

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1012151616910

Navigation