BibTex format
@article{Morello:2006:10.4049/jimmunol.177.10.7173,
author = {Morello, S and Ito, K and Yamamura, S and Lee, KY and Jazrawi, E and DeSouza, P and Barnes, P and Cicala, C and Adcock, IM},
doi = {10.4049/jimmunol.177.10.7173},
journal = {Journal of Immunology},
pages = {7173--7183},
title = {IL-1β and TNF-α regulation of the adenosine receptor (A 2A) expression: Differential requirement for NF-κB binding to the proximal promoter},
url = {http://dx.doi.org/10.4049/jimmunol.177.10.7173},
volume = {177},
year = {2006}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Adenosine is a potent endogenous regulator of airway inflammation that acts through specific receptor subtypes that can either cause constriction (A <inf>1</inf>R, A<inf>2B</inf>R, and A<inf>3</inf>R) or relaxation (A <inf>2A</inf>R) of the airways. We therefore examined the effects of key inflammatory mediators on the expression of the A<inf>2A</inf>R in a lung epithelial cell line (A549). IL-1β and TNF-α increased the expression of the A<inf>2A</inf>R gene at the mRNA and protein levels. In contrast, LPS had no effect on A<inf>2A</inf>R gene expression. IL-1β and TNF-α rapidly activated p50 and p65, but not C-Rel, RelB, or p52, and both IL-1β- and TNF-α-stimulated A<inf>2A</inf>R expression was inhibited by the IκB kinase 2 inhibitor AS602868 in a concentration-dependent manner. Using chromatin immunoprecipitation assays, we demonstrate that IL-1β can enhance p65 association with putative κB binding sites in the A <inf>2A</inf>R promoter in a temporal manner. In contrast, TNF-α failed to enhance p65 binding to these putative sites. Functionally, the two most 5′ κB sites were important for IL-1β-, but not TNF-α-, induced A<inf>2A</inf>R promoter reporter gene activity. Finally, neither TNF-α nor Il-1β had any effect on A<inf>2A</inf>R mRNA transcript degradation. These results directly implicate a major role for NF-κB in the regulation of A<inf>2A</inf>R gene transcription by IL-1β and TNF-α but suggest that the effects of TNF-α on A<inf>2A</inf>R gene transcription are not mediated through the proximal promoter. Copyright © 2006 by The American Association of Immunologists, Inc.
AU - Morello,S
AU - Ito,K
AU - Yamamura,S
AU - Lee,KY
AU - Jazrawi,E
AU - DeSouza,P
AU - Barnes,P
AU - Cicala,C
AU - Adcock,IM
DO - 10.4049/jimmunol.177.10.7173
EP - 7183
PY - 2006///
SN - 0022-1767
SP - 7173
TI - IL-1β and TNF-α regulation of the adenosine receptor (A 2A) expression: Differential requirement for NF-κB binding to the proximal promoter
T2 - Journal of Immunology
UR - http://dx.doi.org/10.4049/jimmunol.177.10.7173
VL - 177
ER -