Anti-inflammatory and corticosteroid-enhancing actions of vitamin D in monocytes of patients with steroid-resistant and those with steroid-sensitive asthma - 29/05/14
Abstract |
Background |
Vitamin D is known for its anti-inflammatory effects.
Objective |
Vitamin D regulation of responses in patients with steroid-resistant (SR) versus steroid-sensitive (SS) asthma has not been studied.
Methods |
Peripheral blood cells from 11 patients with SR asthma and 8 patients with SS asthma were preincubated with 1,25-dihydroxyvitamin D (1,25[OH]2D [VitD]), followed by dexamethasone (DEX) treatment and LPS stimulation. LPS-induced phosphorylated p38 mitogen-activated protein kinase (p-p38) in monocytes was examined by means of flow cytometry. Mitogen-activated protein kinase phosphatase-1 (MKP-1) mRNA expression, which inhibits p-p38, was analyzed by means of real-time PCR. Glucocorticoid receptor (GR) binding and histone H4 acetylation in the glucocorticoid response element of the MKP-1 promoter in monocytes were analyzed by means of chromatin immunoprecipitation.
Results |
DEX significantly inhibited LPS-induced p-p38 in monocytes from patients with SS asthma but not those from patients with SR asthma (P < .01). VitD inhibited LPS-induced p-p38 in monocytes from both patient groups (P < .01) but enhanced DEX suppression of LPS-induced p-p38 only in monocytes from patients with SS asthma (P < .01). VitD induced MKP-1 expression and enhanced DEX induction of MKP-1 in both patients with SS asthma and patients with SR asthma. VitD/DEX-induced MKP-1 mRNA levels remained significantly lower in monocytes from patients with SR asthma (P < .05). DEX-stimulated recruitment of GR and histone H4 acetylation at the glucocorticoid response element 4.6 kbp upstream of the MKP-1 gene were significantly lower in monocytes from patients with SR asthma compared with those from patients with SS asthma. VitD pretreatment enhanced DEX-induced GR binding and histone acetylation in monocytes from both patient groups. However, GR binding and histone H4 acetylation remained significantly lower in monocytes from patients with SR asthma.
Conclusion |
VitD demonstrated anti-inflammatory and corticosteroid-enhancing effects in monocytes of patients with SR asthma and patients with SS asthma. However, the responses to corticosteroids in patients with SR asthma remained significantly lower than those in patients with SS asthma.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, steroid resistance, corticosteroids, vitamin D
Abbreviations used : ChIP, DEX, GR, GRE, MAPK, MED14, MKP-1, p-p38, VitD
Plan
| Supported by National Institutes of Health grants AI070140, 2R56AI070140, and HL37260 and NIH/NCATS Colorado CTSI grant no. UL1 TR001082. This work was also supported by the Edelstein Family Foundation. |
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| Disclosure of potential conflict of interest: Y. Zhang, D. Y. M. Leung, and E. Goleva have received grants from the National Institutes of Health. |
Vol 133 - N° 6
P. 1744 - juin 2014 Retour au numéro
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