Background: Steroid resistant (SR) asthma is characterized by persistent airway inflammation that fails to resolve\ndespite treatment with high doses of corticosteroids. Furthermore, SR patient airways show increased numbers\nneutrophils, which are less responsive to glucocorticoid. The present study seeks to determine whether\ndexamethasone (DEX) has different effect on neutrophils from steroid sensitive (SS) asthmatics compared\nto SR asthmatics.\nMethods: Adults with asthma (n = 38) were classified as SR or SS based on changes in lung FEV1% following\na one-month inhaled corticosteroid (ICS) treatment. Blood samples were collected from all patients during their\nfirst visit of the study. Neutrophils isolated from the blood were cultured with dexamethasone and/or atopic\nasthmatic serum for 18 h. The mRNA expression of mitogen-activated protein kinase phosphatase-1 (MKP-1),\na glucocorticoid transactivation target, and glucocorticoid-induced transcript 1 (GLCCI1), an early marker of\nglucocorticoid-induced apoptosis whose expression was associated with the response to inhaled glucocorticoids\nin asthma , was determined by real-time PCR, and ELISA was used to assess the pro-inflammatory cytokine IL-8\nlevels in the supernatant. Constitutive neutrophil apoptosis was detected by flow cytometry.\nResults: DEX significantly induced MKP-1 expression in both patients with SS and SR patients in a concentrationdependent\nmanner, but greater induction was observed for SS patients at a low concentration (10âË?â??6 M).\nAsthmatic serum alone showed no MKP-1expression, and there was impaired induction of MKP-1 by DEX in SR\nasthma patients. The expression of GLCCI1 was not induced in neutrophils with DEX or DEX/atopic asthmatic\nserum combination. Greater inhibition of IL-8 production was observed in neutrophils from patients with SS\nasthma treated with DEX/atopic asthmatic serum combination compared with SR asthma patients, though DEX\nalone showed the same effect on neutrophils from SS and SR asthma patients. Meanwhile, DEX dependent\ninhibition of constitutive neutrophil apoptosis was similar between SS asthma and SR asthma patients.\nConclusions: DEX exerted different effects on neutrophils from patients with SS asthma and SR asthma, which\nmay contribute to glucocorticoid insensitivity.
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