Anti-inflammatory and corticosteroid-enhancing actions of vitamin D in monocytes of patients with steroid-resistant and those with steroid-sensitive asthma

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Presentation transcript:

Anti-inflammatory and corticosteroid-enhancing actions of vitamin D in monocytes of patients with steroid-resistant and those with steroid-sensitive asthma Yong Zhang, PhD, Donald Y.M. Leung, MD, PhD, Elena Goleva, PhD Journal of Allergy and Clinical Immunology Volume 133, Issue 6, Pages 1744-1752.e1 (June 2014) DOI: 10.1016/j.jaci.2013.12.004 Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 A and B, VitD enhances DEX inhibition of LPS-induced p38 phosphorylation in monocytes from patients with SS asthma (n = 8) (Fig 1, A) but not those from patients with SR asthma (n = 9) (Fig 1, B), as shown by means of flow cytometry. C, Representative flow cytometric data on the effects VitD, DEX, and VitD plus DEX on LPS-induced p-p38 in CD14+ cells from patients with SS asthma and patients with SR asthma are shown. Journal of Allergy and Clinical Immunology 2014 133, 1744-1752.e1DOI: (10.1016/j.jaci.2013.12.004) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 VitD enhances DEX inhibition of LPS-induced IL-6 production in monocytes from patients with SS asthma and patients with SR asthma, as detected by means of ELISA. Percentages of LPS-induced IL-6 levels for each treatment condition compared with the amount of IL-6 produced in response to LPS alone (100%) are shown (n = 5 patients with SR asthma and n = 5 patients with SS asthma). Journal of Allergy and Clinical Immunology 2014 133, 1744-1752.e1DOI: (10.1016/j.jaci.2013.12.004) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 A and B, VitD enhances DEX induction of MKP-1 in monocytes from patients with SS asthma and patients with SR asthma. PBMCs from patients with SS asthma (Fig 3, A) and patients with SR asthma (Fig 3, B) were preincubated with 10 nmol/L VitD for 21 hours, followed by DEX treatment at 10 nmol/L for 3 hours. An adherent PBMC fraction was collected. MKP-1 mRNA levels were detected by using real-time PCR and normalized to β-actin mRNA (n = 8 patients with SR asthma and n = 8 patients with SS asthma). C, MKP-1 induction by DEX and VitD+DEX was significantly greater in cells from SS asthma patients. Journal of Allergy and Clinical Immunology 2014 133, 1744-1752.e1DOI: (10.1016/j.jaci.2013.12.004) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Differential recruitment of GR to the GRE in the MKP-1 gene promoter in monocytes from patients with SS asthma and patients with SR asthma. A, Schematic representation of GR binding to GRE 4.6 and histone acetylation in the human MKP-1 promoter. The number represents kilobase pairs upstream of the transcriptional start site (TSS). B and C, Recruitment of GR (Fig 4, B) and histone H4 acetylation (Fig 4, C) at the GRE 4.6 site (n = 3). Journal of Allergy and Clinical Immunology 2014 133, 1744-1752.e1DOI: (10.1016/j.jaci.2013.12.004) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 S211 GR phosphorylation in response to DEX with and without VitD pretreatment in cells of patients with SS asthma and patients with SR asthma. A, Results from a representative Western blot comparing monocytes from patients with SR asthma and patients with SS asthma are shown out of 5 patients with SR asthma and 5 patients with SS asthma studied. B, Blotting densitometric readings summary of GR S211 phosphorylation normalized to total GR levels. Journal of Allergy and Clinical Immunology 2014 133, 1744-1752.e1DOI: (10.1016/j.jaci.2013.12.004) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Prebronchodilator FEV1 percent predicted before and after a 1-week oral prednisone burst in patients with SR asthma (A) and patients with SS asthma (B). Journal of Allergy and Clinical Immunology 2014 133, 1744-1752.e1DOI: (10.1016/j.jaci.2013.12.004) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions