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Citations to this article

Corticosteroid-resistant bronchial asthma is associated with increased c-fos expression in monocytes and T lymphocytes.
S J Lane, … , P J Barnes, T H Lee
S J Lane, … , P J Barnes, T H Lee
Published December 15, 1998
Citation Information: J Clin Invest. 1998;102(12):2156-2164. https://doi.org/10.1172/JCI2680.
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Research Article Article has an altmetric score of 9

Corticosteroid-resistant bronchial asthma is associated with increased c-fos expression in monocytes and T lymphocytes.

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Abstract

Unstimulated peripheral blood mononuclear cells (PBMCs) from corticosteroid-resistant (CR) but not corticosteroid-sensitive (CS) asthmatics demonstrate increased activating peptide-1 (AP-1)- and decreased glucocorticoid receptor (GR)-DNA binding. We test whether these abnormalities are associated with excessive generation of c-fos, the inducible component of AP-1. The c-fos transcription rate, mRNA and protein levels, and GR-DNA binding were quantitated in PBMCs, T cells, and monocytes from CS, CR, and nonasthmatic subjects. There was a 1.7-, 4.2-, and 2.3-fold greater increase in the baseline c-fos transcription rate, mRNA expression, and protein levels, respectively, in PBMCs derived from CR compared with CS patients. At optimal stimulation with PMA, there was a 5.7-, 3.4-, and 2-fold greater increase in the c-fos transcription rate, mRNA accumulation, and protein levels, respectively, in CR compared with CS PBMCs. These abnormalities were detected in both the T cell and monocyte subpopulations. PMA stimulation converted PBMCs from a CS to a CR phenotype and was associated with direct interaction between c-Fos and the GR. Pretreatment of PBMCs from CR patients with c-fos antisense oligonucleotides enhanced GR-DNA binding activity in CR PBMCs stimulated with dexamethasone. We suggest that increased c-fos synthesis provides a major mechanism for the increased AP-1- and decreased GR- DNA binding seen in CR asthma.

Authors

S J Lane, I M Adcock, D Richards, C Hawrylowicz, P J Barnes, T H Lee

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Total citations by year

Year: 2024 2023 2020 2019 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 Total
Citations: 1 2 1 2 3 2 4 3 2 1 5 7 8 1 2 7 11 5 13 9 7 8 3 107
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Citations to this article in year 2012 (1)

Title and authors Publication Year
Glucocorticoid-resistant asthma and novel anti-inflammatory drugs
CR Keenan, S Salem, ER Fietz, RC Gualano, AG Stewart
Drug Discovery Today 2012

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Referenced in 3 Wikipedia pages
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