FASEB J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by ZHOU, Z.-H. L.
Right arrow Articles by RANSOHOFF, R. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by ZHOU, Z.-H. L.
Right arrow Articles by RANSOHOFF, R. M.
(The FASEB Journal. 2001;15:383-392.)
© 2001 FASEB

Regulation of monocyte chemoattractant protein (MCP)-1 transcription by interferon-gamma (IFN-{gamma}) in human astrocytoma cells: postinduction refractory state of the gene, governed by its upstream elements

Z.-H. LUCY ZHOU1, YULONG HAN, TAO WEI, SUMER ARAS2, PRIYA CHATURVEDI3, SARAH TYLER4, M. R. SANDHYA RANI and RICHARD M. RANSOHOFF*5

Department of Neurosciences, The Lerner Research Institute, and
* Department of Neurology and The Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA

5Correspondence: Department of Neurosciences, Lerner Research Institute, NC30, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, USA. E-mail: ransohr{at}ccf.org

Monocyte chemoattractant protein (MCP)-1 is expressed by astrocytes in diverse inflammatory states and is a key regulator of monocyte recruitment to the central nervous system (CNS). In the current study, we addressed mechanisms by which transcription of the human MCP-1 gene (hMCP-1) was terminated, after induction by interferon (IFN)-{gamma}. Our results demonstrated that IFN-{gamma}-induced transcription of hMCP-1 was followed by a refractory state, during which hMCP-1 was resistant to restimulation by either IFN-{gamma} or heterologous activators such as TNF-{alpha}. This refractory state affected the hMCP-1 gene selectively, as other IFN-{gamma}-inducible genes remained responsive to restimulation. The IFN-{gamma}-induced hMCP-1 refractory state was governed at the transcriptional level and was sensitive to protein synthesis inhibitors, suggesting a requirement for newly expressed components. A minimal 213 base pair hMCP-1 regulatory element directed both IFN-{gamma}-mediated transcription and the subsequent refractory state. We previously demonstrated that IFN-{gamma} treatment resulted in coordinate protein occupancy in vivo of two hMCP-1 promoter elements, a gamma-activated site (GAS) and a GC-rich element. During the refractory state, IFN-{gamma} treatment failed to induce protection of either the hMCP-1 GAS element or the GC box. These results furnish insight into the expression of hMCP-1 during CNS inflammation and provide the first delineation of an IFN-{gamma}-induced transcriptional refractory state.—Zhou, Z.-H. L., Han, Y., Wei, T., Aras, S., Chaturvedi, P., Tyler, S., Rani, M. R. S., Ransohoff, R. M. Regulation of monocyte chemoattractant protein (MCP)-1 transcription by interferon-gamma (IFN-{gamma}) in human astrocytoma cells: postinduction refractory state of the gene, governed by its upstream elements.


Key Words: chemokine • gene expression • interferons • STAT factors • Sp1 transcription factor






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2001 by The Federation of American Societies for Experimental Biology.