HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 286/3/L554    most recent 00191.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Odoms, K. Articles by Wong, H. R. Search for Related Content PubMed PubMed Citation Articles by Odoms, K. Articles by Wong, H. R.

Short-term modulation of interleukin-1 signaling by hyperoxia: uncoupling of IB kinase activation and NF-B-dependent gene expression

Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Children's Hospital Research Foundation, Cincinnati, Ohio 45229

Submitted 16 June 2003 ; accepted in final form 12 November 2003

We have been interested in elucidating how simultaneous stimuli modulate inflammation-related signal transduction pathways in lung parenchymal cells. We previously demonstrated that exposing respiratory epithelial cells to 95% oxygen (hyperoxia) synergistically increased tumor necrosis factor- (TNF-)-mediated activation of NF-B and NF-B-dependent gene expression by a mechanism involving increased activation of IB kinase (IKK). Because the signal transduction mechanisms induced by IL-1 are distinct to that of TNF-, herein we sought to determine whether hyperoxia modulates IL-1-dependent signal transduction. In A549 cells, simultaneous treatment with hyperoxia and IL-1 caused increased activation of IKK, prolonged the degradation of IB, and prolonged the nuclear translocation and DNA binding of NF-B compared with cells treated with IL-1 alone in room air. Hyperoxia did not affect IL-1-dependent degradation of the interleukin receptor-associated kinase differently from treatment with IL- alone. In contrast to the effects on the IKK/IB/NF-B pathway, simultaneous treatment with hyperoxia and IL-1 did not augment NF-B-dependent gene expression compared with treatment with IL-1 alone. Similar observations were made in a different human respiratory epithelial cell line, BEAS-2B cells. In addition, simultaneous treatment with hyperoxia and IL-1 caused hyperphosphorlyation of the NF-B p65 subunit compared with treatment with IL-1 alone. In summary, concomitant treatment of A549 cells with hyperoxia and IL-1 augments activation of IKK, prolongs degradation of IB, and prolongs nuclear translocation and DNA binding of NF-B. This activation, however, is not coupled to increased expression of NF-B-dependent genes, and the mechanism of this decoupling is not related to decreased phosphorylation of p65.

cell signaling; oxidant stress; transcription factors; lung epithelium

This article has been cited by other articles:

				C. J. Wright, T. Zhuang, P. La, G. Yang, and P. A. Dennery Hyperoxia-induced NF-{kappa}B activation occurs via a maturationally sensitive atypical pathway Am J Physiol Lung Cell Mol Physiol, March 1, 2009; 296(3): L296 - L306. [Abstract] [Full Text] [PDF]

				J. P. Bridges, Y. Xu, C.-L. Na, H. R. Wong, and T. E. Weaver Adaptation and increased susceptibility to infection associated with constitutive expression of misfolded SP-C J. Cell Biol., January 30, 2006; 172(3): 395 - 407. [Abstract] [Full Text] [PDF]