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GM-CSF expression in pulmonary epithelial cells Is regulated negatively by posttranscriptional mechanisms

GM-CSF expression in pulmonary epithelial cells Is regulated negatively by posttranscriptional mechanisms
GM-CSF expression in pulmonary epithelial cells Is regulated negatively by posttranscriptional mechanisms
Incubation of pulmonary A549 cells with D609, a phosphatidyl-choline specific phospholipase C (PC-PLC)-inhibitor, or the anti-oxidant, pyrrolidine dithiocarbamate (PTDC), markedly increased IL-1?-induced GM-CSF elaboration. This effect was observed at the mRNA level and could be partially reproduced by the protein synthesis inhibitor, cycloheximide. Following the peak in GM-CSF mRNA, the mRNA half-life (t1/2) was 0.5–1 h. This was increased to around 3 h by cycloheximide, whilst following D609 or PDTC treatment there was essentially no degradation. These data suggest the existence of inhibitory pathways that posttranscriptionally regulate GM-CSF expression via new protein synthesis and D609- and PDTC-sensitive steps. These observations may have important clinical implications. First, drugs that target gene induction may also knock out these inhibitory pathways to lessen their effect. Second, defects in such pathways could lead to overexpression of cytokines or growth factors and contribute to the pathogenesis of inflammatory or proliferative diseases
0006-291X
249-253
Newton, Robert
4a2c2a99-b7ad-4373-8840-96fbb5b5313e
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Hart, Lorraine
93604adc-ff1d-4f59-be0e-baf9826867a4
Barnes, Peter J.
6cbf850c-3499-4e23-983c-4442643c0004
Bergmann, Martin W.
569898b9-1e22-497d-964b-85bb6741f48c
Newton, Robert
4a2c2a99-b7ad-4373-8840-96fbb5b5313e
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Hart, Lorraine
93604adc-ff1d-4f59-be0e-baf9826867a4
Barnes, Peter J.
6cbf850c-3499-4e23-983c-4442643c0004
Bergmann, Martin W.
569898b9-1e22-497d-964b-85bb6741f48c

Newton, Robert, Staples, Karl J., Hart, Lorraine, Barnes, Peter J. and Bergmann, Martin W. (2001) GM-CSF expression in pulmonary epithelial cells Is regulated negatively by posttranscriptional mechanisms. Biochemical and Biophysical Research Communications, 287 (1), 249-253. (doi:10.1006/bbrc.2001.5569). (PMID:11549282)

Record type: Article

Abstract

Incubation of pulmonary A549 cells with D609, a phosphatidyl-choline specific phospholipase C (PC-PLC)-inhibitor, or the anti-oxidant, pyrrolidine dithiocarbamate (PTDC), markedly increased IL-1?-induced GM-CSF elaboration. This effect was observed at the mRNA level and could be partially reproduced by the protein synthesis inhibitor, cycloheximide. Following the peak in GM-CSF mRNA, the mRNA half-life (t1/2) was 0.5–1 h. This was increased to around 3 h by cycloheximide, whilst following D609 or PDTC treatment there was essentially no degradation. These data suggest the existence of inhibitory pathways that posttranscriptionally regulate GM-CSF expression via new protein synthesis and D609- and PDTC-sensitive steps. These observations may have important clinical implications. First, drugs that target gene induction may also knock out these inhibitory pathways to lessen their effect. Second, defects in such pathways could lead to overexpression of cytokines or growth factors and contribute to the pathogenesis of inflammatory or proliferative diseases

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Published date: September 2001
Organisations: Faculty of Medicine

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Local EPrints ID: 374411
URI: http://eprints.soton.ac.uk/id/eprint/374411
ISSN: 0006-291X
PURE UUID: a49c2026-d2a8-4654-a06c-8224fda703fc
ORCID for Karl J. Staples: ORCID iD orcid.org/0000-0003-3844-6457

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Date deposited: 16 Feb 2015 14:12
Last modified: 20 Jul 2019 00:53

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Contributors

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

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