UNSPECIFIED (2001) GM-CSF expression in pulmonary epithelial cells is regulated negatively by posttranscriptional mechanisms. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 287 (1). pp. 249-253. ISSN 0006-291X

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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 beta -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 (t(1/2)) 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. (C) 2001 Academic Press.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology
Journal or Publication Title:	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Publisher:	ACADEMIC PRESS INC
ISSN:	0006-291X
Date:	14 September 2001
Volume:	287
Number:	1
Number of Pages:	5
Page Range:	pp. 249-253
Publication Status:	Published
URI:	http://wrap.warwick.ac.uk/id/eprint/11753

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