Tumor necrosis factor alpha (TNF-α) autoregulates its expression and induces adhesion molecule expression in asthma

Babu, Suresh K., Puddicombe, Sarah M., Arshad, Hasan S., Wilson, Susan J., Ward, Jonathan, Gozzard, Neil, Higgs, Gerry, Holgate, Stephen T. and Davies, Donna E. (2011) Tumor necrosis factor alpha (TNF-α) autoregulates its expression and induces adhesion molecule expression in asthma. Clinical Immunology, 140 (1), 18-25. (doi:10.1016/j.clim.2011.03.005). (PMID:21459047)

Abstract

Subjects with mild asthma underwent repeated low-dose allergen exposure and bronchial biopsies were examined for the expression of TNF-α and adhesion molecules. Bronchial biopsies from moderately severe asthmatics were then tested in an explant culture system to assess the effect of Der p and CDP-870, a TNF-α blocking pegylated-antibody Fab, on expression of TNF-α and adhesion molecules. Low-dose allergen challenge significantly upregulated sub-mucosal mast cells, TNF-α+ cells, and VCAM. When bronchial explants were exposed to Der p and CDP 870 for 24 h, CDP 870 caused a significant reduction in TNF-α release both at baseline and following stimulation with Der p allergen. The bronchial biopsies showed significant upregulation of TNF-α positive cells and ICAM-1 following exposure to Der p (p = 0.03) and this was reduced in the presence of CDP-870. So, allergen exposure up-regulates TNF-α expression in asthma and down-stream targets, including adhesion molecules that contribute to airway inflammation.

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Contributors

Author: Susan J. Wilson

Author: Jonathan Ward

Author: Donna E. Davies

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