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J Allergy Clin Immunol. 2006 Aug;118(2):368-75. Epub 2006 Jun 27.

Systemic glucocorticoid reduces bronchial mucosal activation of activator protein 1 components in glucocorticoid-sensitive but not glucocorticoid-resistant asthmatic patients.

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King's College London, MRC, London SE1 9RT.



Overexpression of the transcriptional regulatory factor activator protein 1 might contribute to T-cell glucocorticoid (GC) refractoriness in GC-resistant asthma.


We sought to address the hypothesis that clinically GC-resistant asthma is accompanied by failure of systemic GCs to inhibit phosphorylation of c-jun and c-jun N-terminal kinase (JNK) in bronchial mucosal cells.


We performed enumeration of total (CD45+) leukocytes and cells expressing c-fos and total and phosphorylated c-jun and JNK in bronchial biopsy sections from 9 GC-sensitive and 17 GC-resistant asthmatic patients taken before and after oral prednisolone (40 mg/1.72 m(2) body surface area daily for 14 days) using specific antibodies, immunohistochemistry, and image analysis.


At baseline, mean total (CD45+) mucosal leukocytes, total cells expressing phosphorylated c-jun and JNK, and mean percentages of cells in which these molecules were phosphorylated were similar in both groups, whereas mean total numbers of c-fos-immunoreactive cells were increased in the GC-resistant asthmatic subjects (P = .04). After prednisolone, the mean total cells expressing phosphorylated c-jun and JNK and the mean percentages of cells in which these molecules were phosphorylated were significantly reduced in the GC-sensitive (P < or = .02) but not the GC-resistant asthmatic subjects. Mean total CD45+ leukocytes and c-fos-immunoreactive cells were not significantly altered in either group.


Clinical GC responsiveness in asthma is accompanied by reduced phosphorylation of bronchial mucosal c-jun and JNK, a phenomenon not seen in resistant patients.


Dysregulation of activator protein 1 activation leading to clinical GC resistance might reflect identifiable environmental influences and is a target for future therapy.

[Indexed for MEDLINE]

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