HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Garcia, C. S. Articles by Espinoza-Delgado, I. Search for Related Content PubMed PubMed Citation Articles by Garcia, C. S. Articles by Espinoza-Delgado, I.

The Antineoplastic Agent Bryostatin-1 Differentially Regulates IFN- Receptor Subunits in Monocytic Cells: Transcriptional and Posttranscriptional Control of IFN-R2¹

Carmen S. Garcia^2,*, Rafael E. Curiel^2,*, James M. Mwatibo^*, Sidney Pestka, Huifen Li and Igor Espinoza-Delgado^3,

^* Department of Medicine and Stanley S. Scott Cancer Center, Louisiana State University Medical Center, New Orleans, LA 70112; Department of Molecular Genetics and Microbiology, Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854; and Hematology-Oncology Section, Gerontology Research Center, National Institute on Aging, Baltimore, MD 21224

Bryostatin-1 (Bryo-1) is a potent ligand and modulator of protein kinase C that exerts antineoplastic and immunomodulatory activities both in vitro and in vivo. We have previously reported that Bryo-1 synergized with IFN- to induce NO synthase and NO by macrophages. To determine whether this effect was associated with changes in levels of IFN-R, we investigated the effects of Bryo-1 on the expression and regulation of IFN-R chains in monocytic cells. Northern blot analysis revealed that Bryo-1 treatment of the human monocytic cell lines MonoMac6 and THP-1 and human monocytes enhanced the expression of IFN-R2 mRNA but did not affect IFN-R1 mRNA expression. Bryo-1 increased IFN-R2 mRNA in a dose-dependent manner as early as 3 h posttreatment. Bryo-1-induced up-regulation of IFN-R2 mRNA levels is not dependent on de novo protein synthesis as shown by cell treatment with the protein-synthesis inhibitor cycloheximide. Bryo-1 treatment increased the IFN-R2 mRNA half-life by 2 h. EMSA analysis from Bryo-1-treated MonoMac6 cells showed an increased nuclear protein binding to the NF-B motif present in the 5' flanking region of the human IFN-R2 promoter that was markedly decreased by pretreatment with the NF-B inhibitor SN50. These results show for the first time that Bryo-1 up-regulates IFN-R2 expression in monocytic cells. Given the pivotal role that IFN- exerts on monocyte activation and in the initiation and outcome of the immune response, the induction of IFN-R2 by Bryo-1 has significant implications in immunomodulation and could overcome some of the immune defects observed in cancer patients.