The University of Southampton
University of Southampton Institutional Repository

Nuclear factor-kappaB does not mediate the inhibitory effects of dexamethasone on granulocyte-macrophage colony-stimulating factor expression

Nuclear factor-kappaB does not mediate the inhibitory effects of dexamethasone on granulocyte-macrophage colony-stimulating factor expression
Nuclear factor-kappaB does not mediate the inhibitory effects of dexamethasone on granulocyte-macrophage colony-stimulating factor expression
Human granulocyte–macrophage colony-stimulating factor (GM-CSF) reporter constructs containing up to 3·3 kb of upstream promoter sequence were transiently transfected into both Jurkat and HUT78 human T-cell lines. In Jurkat cells, stimulation with phorbol 12-myristate 13-acetate (PMA) plus phytohemaglutinin (PHA) produced robust increases in reporter activity, whereas HUT78 cells showed low levels of reporter induction attributable to constitutive nuclear factor (NF)-?B activity. Following mutation of either the proximal NF-?B site (?85/?76) or the activator protein1 (AP-1) motif within the conserved lymphokine element 0 (CLE0) site (?54/?31), reporter activity was markedly reduced in both cell lines. Despite this dependence on NF-?B and CLE0/AP-1, GM-CSF reporter activity was unaffected by dexamethasone in either cell line. Similarly, an NF-?B-dependent reporter was also not repressed by dexamethasone, yet GM-CSF release from HUT78 T cells was inhibited. These data therefore confirm a critical role for both NF-?B and CLE0 sites in GM-CSF promoter activation and indicate that NF-?B may not mediate glucocorticoid-dependent repression of GM-CSF in these cells
0019-2805
430-434
Bergmann, Martin W.
569898b9-1e22-497d-964b-85bb6741f48c
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Barnes, Peter J.
6cbf850c-3499-4e23-983c-4442643c0004
Newton, Robert
4a2c2a99-b7ad-4373-8840-96fbb5b5313e
Bergmann, Martin W.
569898b9-1e22-497d-964b-85bb6741f48c
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Barnes, Peter J.
6cbf850c-3499-4e23-983c-4442643c0004
Newton, Robert
4a2c2a99-b7ad-4373-8840-96fbb5b5313e

Bergmann, Martin W., Staples, Karl J., Barnes, Peter J. and Newton, Robert (2004) Nuclear factor-kappaB does not mediate the inhibitory effects of dexamethasone on granulocyte-macrophage colony-stimulating factor expression. Immunology, 111 (4), 430-434. (doi:10.1111/j.0019-2805.2004.01833.x).

Record type: Article

Abstract

Human granulocyte–macrophage colony-stimulating factor (GM-CSF) reporter constructs containing up to 3·3 kb of upstream promoter sequence were transiently transfected into both Jurkat and HUT78 human T-cell lines. In Jurkat cells, stimulation with phorbol 12-myristate 13-acetate (PMA) plus phytohemaglutinin (PHA) produced robust increases in reporter activity, whereas HUT78 cells showed low levels of reporter induction attributable to constitutive nuclear factor (NF)-?B activity. Following mutation of either the proximal NF-?B site (?85/?76) or the activator protein1 (AP-1) motif within the conserved lymphokine element 0 (CLE0) site (?54/?31), reporter activity was markedly reduced in both cell lines. Despite this dependence on NF-?B and CLE0/AP-1, GM-CSF reporter activity was unaffected by dexamethasone in either cell line. Similarly, an NF-?B-dependent reporter was also not repressed by dexamethasone, yet GM-CSF release from HUT78 T cells was inhibited. These data therefore confirm a critical role for both NF-?B and CLE0 sites in GM-CSF promoter activation and indicate that NF-?B may not mediate glucocorticoid-dependent repression of GM-CSF in these cells

Full text not available from this repository.

More information

Published date: 30 March 2004
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 374401
URI: https://eprints.soton.ac.uk/id/eprint/374401
ISSN: 0019-2805
PURE UUID: 989f0f39-c293-48cf-b0a5-77df6576abc2
ORCID for Karl J. Staples: ORCID iD orcid.org/0000-0003-3844-6457

Catalogue record

Date deposited: 16 Feb 2015 11:46
Last modified: 06 Jun 2018 12:39

Export record

Altmetrics

Contributors

Author: Martin W. Bergmann
Author: Karl J. Staples ORCID iD
Author: Peter J. Barnes
Author: Robert Newton

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×