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Leukotriene D(4) induces AP-1 but not NFkappaB signaling in intestinal epithelial cells.

Bengtsson, Astrid LU ; Massoumi, Ramin LU and Sjölander, Anita LU (2008) In Prostaglandins & other Lipid Mediators 85(3-4). p.100-106
Abstract
We have previously shown that leukotriene D(4) (LTD(4)), a known pro-inflammatory mediator, induces increased survival and proliferation of intestinal epithelial cells. In this study we examined whether LTD(4) functions via activation of the transcription factors NFkappaB and AP-1, which are potent inducers of mitogenesis. We found that the NFkappaB inhibitory protein IkappaBalpha was not degraded upon LTD(4) stimulation. Furthermore, nuclear translocation of the classical p65 or alternative p52 subunits of NFkappaB was not observed. Accordingly, LTD(4) stimulation failed to induce NFkappaB transcriptional activity. Instead we found that LTD(4) induced phosphorylation of c-Jun-N-terminal kinase (JNK) and transcriptional activity of AP-1,... (More)
We have previously shown that leukotriene D(4) (LTD(4)), a known pro-inflammatory mediator, induces increased survival and proliferation of intestinal epithelial cells. In this study we examined whether LTD(4) functions via activation of the transcription factors NFkappaB and AP-1, which are potent inducers of mitogenesis. We found that the NFkappaB inhibitory protein IkappaBalpha was not degraded upon LTD(4) stimulation. Furthermore, nuclear translocation of the classical p65 or alternative p52 subunits of NFkappaB was not observed. Accordingly, LTD(4) stimulation failed to induce NFkappaB transcriptional activity. Instead we found that LTD(4) induced phosphorylation of c-Jun-N-terminal kinase (JNK) and transcriptional activity of AP-1, which could be reduced by a JNK inhibitor. Moreover, LTD(4) induced cell proliferation, and this effect was also blocked upon addition of a JNK inhibitor. Our findings show for the first time that JNK/AP-1 but not NFkappaB is a downstream target of LTD(4) in intestinal epithelial cells, suggesting that AP-1 is an important mediator of LTD(4)-induced mitogenic effects. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Prostaglandins & other Lipid Mediators
volume
85
issue
3-4
pages
100 - 106
publisher
Elsevier
external identifiers
  • pmid:18083053
  • wos:000254823700004
  • scopus:39649116230
ISSN
1098-8823
DOI
10.1016/j.prostaglandins.2007.11.001
language
English
LU publication?
yes
id
d0da4223-1126-4036-b528-cc44ef437cf0 (old id 1035204)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18083053?dopt=Abstract
date added to LUP
2008-02-28 09:07:30
date last changed
2017-01-01 05:24:50
@article{d0da4223-1126-4036-b528-cc44ef437cf0,
  abstract     = {We have previously shown that leukotriene D(4) (LTD(4)), a known pro-inflammatory mediator, induces increased survival and proliferation of intestinal epithelial cells. In this study we examined whether LTD(4) functions via activation of the transcription factors NFkappaB and AP-1, which are potent inducers of mitogenesis. We found that the NFkappaB inhibitory protein IkappaBalpha was not degraded upon LTD(4) stimulation. Furthermore, nuclear translocation of the classical p65 or alternative p52 subunits of NFkappaB was not observed. Accordingly, LTD(4) stimulation failed to induce NFkappaB transcriptional activity. Instead we found that LTD(4) induced phosphorylation of c-Jun-N-terminal kinase (JNK) and transcriptional activity of AP-1, which could be reduced by a JNK inhibitor. Moreover, LTD(4) induced cell proliferation, and this effect was also blocked upon addition of a JNK inhibitor. Our findings show for the first time that JNK/AP-1 but not NFkappaB is a downstream target of LTD(4) in intestinal epithelial cells, suggesting that AP-1 is an important mediator of LTD(4)-induced mitogenic effects.},
  author       = {Bengtsson, Astrid and Massoumi, Ramin and Sjölander, Anita},
  issn         = {1098-8823},
  language     = {eng},
  number       = {3-4},
  pages        = {100--106},
  publisher    = {Elsevier},
  series       = {Prostaglandins & other Lipid Mediators},
  title        = {Leukotriene D(4) induces AP-1 but not NFkappaB signaling in intestinal epithelial cells.},
  url          = {http://dx.doi.org/10.1016/j.prostaglandins.2007.11.001},
  volume       = {85},
  year         = {2008},
}