Adenovirus-mediated murine interferon-gamma receptor transfer enhances the efficacy of IFN-gamma in vivo.

Abstract

Interferon gamma (IFN-gamma) plays an important role in immune response, apoptosis, and anti-tumor activity. Its biological activity depends on expression of IFN-gamma receptor (IFN-gammaR). To address whether increased expression of IFN-gammaR is associated in vivo with a higher biological response by IFN-gamma, we constructed an adenovirus vector including murine IFN-gammaR (Ad-mIFN-gammaR). We confirmed the appropriate function of mIFN-gammaR derived from Ad-mIFN-gammaR based on the observation of signal transduction and transcription. We also found that elevated expression of mIFN-gammaR increases sensitivity to recombinant murine IFN-gamma (rmIFN-gamma) in vitro in target cells. Furthermore, we demonstrated that the growth rate of tumors transfected with Ad-mIFN-gammaR is suppressed in response to rmIFN-gamma in vivo and that such growth suppression is partly due to apoptosis. To our knowledge, this is the first report of adenovirus-mediated IFN-gammaR gene transfer being effective in augmenting the biological activity of IFN-gamma, and the strategy employed in the present study will be useful in studying other kinds of cytokine receptors and applications to gene therapy for cancer and infectious diseases.

• Authors: Yasuto Nishida, Yasushi Maeda, Akio Hara, Toshiyuki Arima, En Kimura, Satoshi Yamashita, Eiichiro Uyama, Shuji Mita, Makoto Uchino
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 290 Issue 3 Pg. 1042-7 (Jan 25 2002) ISSN: 0006-291X [Print] United States
• PMID: 11798180 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Chemokine CXCL10
• Chemokines, CXC
• Interferon-Stimulated Gene Factor 3
• RNA, Messenger
• Receptors, Interferon
• Transcription Factors
• gamma interferon activation factor
• interferon gamma receptor
• Interferon-gamma

Topics

• Adenoviridae (genetics)
• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis
• Cell Division
• Cell Line
• Chemokine CXCL10
• Chemokines, CXC (biosynthesis, genetics)
• Combined Modality Therapy
• Dose-Response Relationship, Drug
• Genetic Therapy
• Genetic Vectors
• Humans
• Interferon-Stimulated Gene Factor 3
• Interferon-gamma (pharmacology)
• Mice
• Neoplasms, Experimental (drug therapy, pathology, therapy)
• RNA, Messenger (biosynthesis)
• Receptors, Interferon (genetics)
• Signal Transduction
• Transcription Factors (metabolism)
• Transfection
• Tumor Cells, Cultured