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Media type:
E-Article
Title:
TGF-β Increases Leukotriene C4 Synthase Expression in the Monocyte-Like Cell Line, THP-1
Contributor:
Riddick, Carl A.;
Serio, Kenneth J.;
Hodulik, Craig R.;
Ring, William L.;
Regan, Mark S.;
Bigby, Timothy D.
imprint:
The American Association of Immunologists, 1999
Published in:The Journal of Immunology
Language:
English
DOI:
10.4049/jimmunol.162.2.1101
ISSN:
0022-1767;
1550-6606
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title><jats:p>The goal of this study was to determine whether cytokines modulate leukotriene C4 (LTC4) synthase expression in mononuclear phagocytes. A panel of cytokines was surveyed for changes in LTC4 synthase mRNA in THP-1 cells. TGF-β1, -2, and -3 had significant stimulatory effects. The addition of TGF-β resulted in a time-dependent increase in LTC4 synthase mRNA at 6 h, which persisted through 48 h. Furthermore, this conditioning resulted in an increase in immunoreactive protein for LTC4 synthase through 7 days. TGF-β conditioning of cells resulted in a time- and dose-dependent increase in stimulated LTC4 synthase activity. Following transient transfection of THP-1 cells with a promoter-reporter construct containing 1.2 kb of the LTC4 synthase promoter, TGF-β treatment resulted in a 2-fold increase in reporter activity. Conditioning with TGF-β did not prolong the half-life of LTC4 synthase mRNA, as assessed by RNase protection assays in actinomycin D-treated cells. Cycloheximide exposure experiments revealed that new protein synthesis was not required for the observed stimulatory effect of TGF-β on LTC4 synthase mRNA. We conclude that LTC4 synthase expression is increased at a transcriptional level by TGF-β in mononuclear phagocytes.</jats:p>