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

In English

Författare

Summary, in English

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.

Publiceringsår

2008

Språk

Engelska

Sidor

100-106

Publikation/Tidskrift/Serie

Prostaglandins & other Lipid Mediators

Volym

85

Issue

3-4

Dokumenttyp

Artikel i tidskrift

Förlag

Elsevier

Ämne

  • Cancer and Oncology

Status

Published

Forskningsgrupp

  • Cell Pathology, Malmö

ISBN/ISSN/Övrigt

  • ISSN: 1098-8823