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Effects of budesonide and formoterol on NF-?B, adhesion molecules, and cytokines in asthma

Effects of budesonide and formoterol on NF-?B, adhesion molecules, and cytokines in asthma
Effects of budesonide and formoterol on NF-?B, adhesion molecules, and cytokines in asthma
The asthmatic inflammatory response can be attenuated by corticosteroids and in part by beta 2-agonists. We investigated if these effects are accompanied by a downregulation in nuclear factor kappa B (NF-kappa B), a transcription factor regulating many of the cytokine and adhesion molecule genes expressed in allergic inflammation. Bronchial biopsies were taken before and after 8 wk treatment with formoterol, budesonide, or placebo from atopic asthmatics. Biopsies were processed into glycol methacrylate and stained immunohistochemically for eosinophils (as an index of inflammation), activated and total NF-kappa B, adhesion molecules, and cytokines. After budesonide treatment there was a significant decrease in the number of submucosal cells staining for total NF-kappa B, granulocyte macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha ), accompanied by a significant decrease in mucosal eosinophils and expression of vascular cell adhesion molecule-1 (VCAM-1) in the endothelium and interleukin-8 (IL-8) in the epithelium. After formoterol treatment there was a significant decrease in eosinophils and the epithelial expression of activated NF-kappa B, but these changes were not accompanied by reduced immunoreactivity for adhesion molecules or cytokines. We conclude that at least some of the therapeutic efficacy of inhaled corticosteroids is mediated through inhibition of NF-kappa B-regulated gene expression, whereas the reduction in airway eosinophilia by long-acting beta 2-agonists probably operates through alternative pathways.
budesonide, formoterol, NF-?B, immunohistochemistry, asthma
1073-449X
1047-1052
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Wallin, Annika
113ea341-ee86-42ed-9afc-8a60d75e8924
Della-Cioppa, Giovanni
20d75b80-a2dc-46e2-8735-4bf2db73bfed
Sandstrom, Thomas
99593b63-fa97-40b6-a57d-5d7b2b4b1c01
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Wallin, Annika
113ea341-ee86-42ed-9afc-8a60d75e8924
Della-Cioppa, Giovanni
20d75b80-a2dc-46e2-8735-4bf2db73bfed
Sandstrom, Thomas
99593b63-fa97-40b6-a57d-5d7b2b4b1c01
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc

Wilson, Susan J., Wallin, Annika, Della-Cioppa, Giovanni, Sandstrom, Thomas and Holgate, Stephen T. (2001) Effects of budesonide and formoterol on NF-?B, adhesion molecules, and cytokines in asthma. American Journal of Respiratory and Critical Care Medicine, 164 (6), 1047-1052. (doi:10.1164/ajrccm.164.6.2010045).

Record type: Article

Abstract

The asthmatic inflammatory response can be attenuated by corticosteroids and in part by beta 2-agonists. We investigated if these effects are accompanied by a downregulation in nuclear factor kappa B (NF-kappa B), a transcription factor regulating many of the cytokine and adhesion molecule genes expressed in allergic inflammation. Bronchial biopsies were taken before and after 8 wk treatment with formoterol, budesonide, or placebo from atopic asthmatics. Biopsies were processed into glycol methacrylate and stained immunohistochemically for eosinophils (as an index of inflammation), activated and total NF-kappa B, adhesion molecules, and cytokines. After budesonide treatment there was a significant decrease in the number of submucosal cells staining for total NF-kappa B, granulocyte macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha ), accompanied by a significant decrease in mucosal eosinophils and expression of vascular cell adhesion molecule-1 (VCAM-1) in the endothelium and interleukin-8 (IL-8) in the epithelium. After formoterol treatment there was a significant decrease in eosinophils and the epithelial expression of activated NF-kappa B, but these changes were not accompanied by reduced immunoreactivity for adhesion molecules or cytokines. We conclude that at least some of the therapeutic efficacy of inhaled corticosteroids is mediated through inhibition of NF-kappa B-regulated gene expression, whereas the reduction in airway eosinophilia by long-acting beta 2-agonists probably operates through alternative pathways.

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Published date: 15 September 2001
Keywords: budesonide, formoterol, NF-?B, immunohistochemistry, asthma

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Local EPrints ID: 27491
URI: https://eprints.soton.ac.uk/id/eprint/27491
ISSN: 1073-449X
PURE UUID: 33ac7d6a-c17a-44c2-80d2-925dc0f235af

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Date deposited: 28 Apr 2006
Last modified: 19 Jul 2019 19:03

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Contributors

Author: Susan J. Wilson
Author: Annika Wallin
Author: Giovanni Della-Cioppa
Author: Thomas Sandstrom

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