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

Published online before print February 3, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.0805466v1 79/4/818    most recent Alert me when this article is cited Alert me if a correction is posted 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, L.-b. Articles by Goleva, E. Search for Related Content PubMed PubMed Citation Articles by Li, L.-b. Articles by Goleva, E.

(Journal of Leukocyte Biology. 2006;79:818-827.)
© 2006 by Society for Leukocyte Biology

Divergent expression and function of glucocorticoid receptor ß in human monocytes and T cells

Ling-bo Li^*, Donald Y. M. Leung^*,,1, Clifton F. Hall^* and Elena Goleva^*

^* Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado; and
Department of Pediatrics, University of Colorado Health Sciences Center, Denver

¹Correspondence: National Jewish Medical and Research Center, 1400 Jackson Street, Room K926i, Denver, CO 80206. E-mail: leungd{at}njc.org

Glucocorticoid (GC) insensitivity is a significant problem in the treatment of immune-mediated diseases. The current study examined whether T cells and monocytes differed in their response to GC and the potential molecular basis for their variation in response to steroids. Functional studies revealed that dexamethasone (DEX) inhibited phorbol 12-myristate 13-acetate/ionomycin-induced tumor necrosis factor and interleukin-6 production to a significantly lesser extent in monocytes than T cells. In parallel, a significantly longer period of time was required for DEX to induce the steroid-responsive gene, mitogen-activated protein kinase phosphatase-1 (MKP-1), in human monocytes as compared with T cells. It is interesting that such differences were not observed between murine T cells and monocytes. GC receptor ß (GCRß) is a splicing variant of the classic GCR, GCR, which functions as a dominant-negative inhibitor of GCR in humans, not mice (as mice do not express GCRß mRNA as a result of a difference in the murine GCR 9b exon sequence). It was found that human monocytes had a significantly higher level of GCRß than T cells. Furthermore, GCRß was found in the cytoplasm and nucleus of monocytes, and GCRß was localized to the nucleus of T cells. This raised the possibility that GCRß in the cytoplasm could affect GCR cellular shuttling in response to DEX. Indeed, we found that DEX-induced nuclear translocation of GCR was decreased in monocytes as compared with T cells. Specific RNA silencing of GCRß in human monocytes resulted in enhanced steroid-induced GCR transactivation and transrepression. Our data suggest that GCRß contributes to variation in the GC responses of monocytes versus T cells.

Key Words: steroid resistance • MKP-1 • dexamethasone

This article has been cited by other articles:

				M. J. M. Schaaf, D. Champagne, I. H. C. van Laanen, D. C. W. A. van Wijk, A. H. Meijer, O. C. Meijer, H. P. Spaink, and M. K. Richardson Discovery of a Functional Glucocorticoid Receptor {beta}-Isoform in Zebrafish Endocrinology, April 1, 2008; 149(4): 1591 - 1599. [Abstract] [Full Text] [PDF]

				L.-b. Li, D. Y. M. Leung, M. J. Strand, and E. Goleva ATF2 impairs glucocorticoid receptor mediated transactivation in human CD8+ T cells Blood, September 1, 2007; 110(5): 1570 - 1577. [Abstract] [Full Text] [PDF]