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Regulation of leukotriene-dependent induction of cyclooxygenase-2 and Bcl-2.

Abstract：

:Leukotrienes play an important pathophysiological role in chronic inflammatory states and, as previously shown, cause increased levels of cyclooxygenase-2 (COX-2) in intestinal epithelial cells. The anti-apoptotic protein Bcl-2 is also elevated by LTD(4) stimulation, and in colon cancer, so we studied the mechanisms of COX-2 and Bcl-2 regulation. We found that LTD(4) induced a 3-fold elevation of COX-2 transcription in Int 407 cells and a 2-fold equivalent in colon cancer cells, Caco-2. This was mediated through a pertussis toxin (PTX) sensitive G-protein and the MAP kinase Erk-1/2 pathway, and this was also shown to be the route to up-regulation of Bcl-2 by LTD(4). In good agreement with this, we detected a strong activation of Erk-1/2 that was further increased by COX-2 inhibition, pointing towards the existence of negative feedback regulation. Furthermore, COX-2 activity is responsible for the effects on Bcl-2, but this is not conveyed through the production of PGE(2).

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Wikström K,Ohd JF,Sjölander A

doi

10.1016/s0006-291x(03)00187-6

subject

Has Abstract

pub_date

2003-03-07 00:00:00

pages

330-5

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006291X03001876

journal_volume

302

pub_type

杂志文章

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