UNSPECIFIED. (2004) ICAM-1 expression is highly NF-kappa B-dependent in A549 cells - No role for ERK and p38 MAPK. EUROPEAN JOURNAL OF BIOCHEMISTRY, 271 (4). pp. 785-791. ISSN 0014-2956

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Abstract

The transcription factor nuclear factor kappaB (NF-kappaB) is an activator of multiple cytokines, chemokines and adhesion molecules, which are important in inflammatory diseases such as asthma, and is consequently considered as an attractive therapeutic target. In the present study, a constitutively active dominant version of IkappaBalpha, IkappaBalphaDN, was introduced into A549 pulmonary cells by adenovirus-mediated delivery. The dominant IkappaB, but not a null viral vector, prevented the induction of NF-kappaB-dependent transcription by both tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta). Similarly, both TNFalpha and IL-1beta strongly induced mRNA and protein expression of intercellular adhesion molecule (ICAM)-1 and in each case this was prevented by adenovirus expressing the dominant IkappaB, but not by the null virus, thereby establishing ICAM-1 as an NF-kappaB-dependent gene. Numerous studies have suggested key roles for the p38 and extracellular regulated kinase (ERK) mitogen-activated protein kinase (MAPK) cascades in the activation and transactivation of NF-kappaB. We show here that SB203580, a selective inhibitor of the p38 MAPK, and PD098059 and UO126, both selective inhibitors of the ERK MAPK cascade, have no effect on TNFalpha or IL-1beta-induced translocation and DNA binding of NF-kappaB. Furthermore, these inhibitors showed no pharmacologically relevant effect on NF-kappaB-dependent transcription nor was there any effect on expression of ICAM-1. Taken together these data highlight the potential use of inhibition of the NF-kappaB signalling pathway in pulmonary inflammatory diseases and suggest that inhibitors of the p38 and ERK MAPK pathways may be of lesser effect.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry
Journal or Publication Title:	EUROPEAN JOURNAL OF BIOCHEMISTRY
Publisher:	BLACKWELL PUBLISHING LTD
ISSN:	0014-2956
Date:	February 2004
Volume:	271
Number:	4
Number of Pages:	7
Page Range:	pp. 785-791
Identification Number:	10.1111/j.1432-1033.2004.03982.x
Publication Status:	Published
URI:	http://wrap.warwick.ac.uk/id/eprint/8801

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