Increased serum VDBP as a risk predictor for steroid resistance in asthma patients

Jiang, H.; Chi, Xiangyu; Zhang, Xuan; Wang, Jing

doi:10.1016/j.rmed.2016.03.011

Cited by 18 publications

(10 citation statements)

References 26 publications

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“…It has been previously showed that higher level of VDBP decreases the bioactivity of Vit D. Gupta et al showed that VDBP increased in biological fluids of children with severe therapy‐resistant asthma and the association between rises in BAL‐VDBP with asthma control was significant. More recently, Jiang et al revealed that VDBP increased in patients with steroid‐resistant asthma as compared to steroid‐sensitive asthma. They proposed that serum VDBP may apply as a useful biomarker for predicting the resistance to steroid in asthma patients.…”

Section: Discussionmentioning

confidence: 99%

Association of vitamin D genetic pathway with asthma susceptibility in the Kurdish population

Nasiri-Kalmarzi

Abdi

Hosseini

et al. 2019

Clinical Laboratory Analysis

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Background Vitamin D (Vit D) function in asthma progression has been studied well. The effects of genetic variations in Vit D pathway molecules have been also studied, although the results are contradicted. In the present study, for the first time we examined the Vit D pathway molecules included serum Vit D and vitamin D‐binding protein (VDBP) and also genetic variations in the vitamin D receptor (VDR) and VDBP in a Kurdish population with asthma. Methods An enzyme‐linked immunosorbent assay (ELISA) method was used to measure the serum Vit D and VDBP. VDR rs1544410 and rs2228570 and VDBP rs7041 were assessed by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Results The serum level of Vit D significantly decreased in asthmatic patients versus controls (16.26 ± 6.76 vs 23.05 ± 10.57 ng/mL, P value = .001). We observed an indirect correlation between Vit D and clinical findings. We also found an increased level of serum VDBP in patients as compared to the controls (1044.6 ± 310.82 vs 545.95 ± 121.73 µg/mL, P value < .0001). Besides, the risk of asthma progression was increased in patients with the VDR rs2228570 CC and VDBP rs7041 GG genotypes (OR = 3.56, P = .0382 and OR = 2.58, P = .01, respectively). Conclusion In summary, our results explain the influence of the genetic variations in VDR and VDBP in addition to Vit D and VDBP serum concentrations on asthma susceptibility in the Kurdish population.

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Section: Discussionmentioning

confidence: 99%

Association of vitamin D genetic pathway with asthma susceptibility in the Kurdish population

Nasiri-Kalmarzi

Abdi

Hosseini

et al. 2019

Clinical Laboratory Analysis

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“…The clinical response of patients to corticosteroid therapy was measured with a PC-based spirometer (WinspiroPRO; Medical International Research). Patients with asthma were defined as SR if they experienced <10% improvement, or as SS if they experienced ≥10% improvement in baseline forced expiratory volume (FEV) in 1 sec after a 14-day course of oral prednisolone (20). In total, 20 patients were diagnosed with SR asthma and 372 patients were diagnosed with SS asthma.…”

Section: Methodsmentioning

confidence: 99%

Interleukin‑35 sensitizes monocytes from patients with asthma to glucocorticoid therapy by regulating p38 MAPK

Qian

Xue

et al. 2020

Exp Ther Med

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The activation of monocytes and macrophages is associated with steroid-resistant (SR) asthma. Interleukin-35 (IL-35) is an important anti-inflammatory cytokine, but its regulatory effects on monocytes in patients with SR asthma is not fully understood. Based on clinical response to oral prednisolone, 34 patients with steroid-sensitive (SS) asthma and 20 patients with SR asthma were enrolled in the present study. Serum IL-35 levels were analyzed using the Luminex 200 platform. Monocytes from patients with asthma were pretreated with IL-35 followed by dexamethasone (DEX) and lipopolysaccharide (LPS), then corticosteroid sensitivity was evaluated according to the half-maximal inhibitory concentration of DEX with respect to LPS-induced IL-6 maximal production in monocytes (DEX-IC 50). The percentage of maximal inhibition of IL-6 by DEX was presented as E max. Phosphorylated-P38 mitogen activated kinase (p-p38 MAPK) and mitogen-activated protein kinase phosphatase-1 (MKP-1) were examined by flow cytometry and reverse transcription-quantitative PCR analysis, respectively. Glucocorticoid receptor (GR) binding to the glucocorticoid response element (GRE) was assessed by chromatin immunoprecipitation. Compared with patients with SS asthma, patients with SR asthma had lower IL-35 expression levels (P<0.05). Correlation analysis results demonstrated that the expression levels of IL-35 showed a weak negative correlation with log DEX-IC 50 (r=-0.351; P<0.01) and a moderate positive correlation with E max value (r=0.4501; P<0.01) in all patients with asthma. Moreover, IL-35 enhanced DEX-suppressed IL-6 production and the DEX-induced upregulation of the MKP-1 mRNA expression level in monocytes from both patient groups (P<0.01). In addition, IL-35 inhibited p-p38 MAPK expression in monocytes, and these effects were mediated via an increase in DEX-induced GR binding to GRE. Therefore, IL-35 may be involved in the corticosteroid enhancing effects in monocytes of patients with SR and SS asthma, suggesting potential benefits of IL-35 supplementation in asthmatics with DEX.

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“…Glucocorticoids (GCs), especially inhaled GCs, became the first-line treatment for asthma because of the prominent anti-inflammatory effect and rapid onset of action [ 6 ]. Inhaled GCs at conventional doses play small roles in severe asthma [ 7 , 8 ], while administration at high doses or in a long term will induce a series of side effects such as growth stunting in children, GC dependent even resistance, and hypothalamic-pituitary-adrenal (HPA) axis dysfunction [ 9 – 11 ]. Improving therapeutic and side effects of GCs through drug combination has a great significance for the treatment of asthma.…”

Section: Introductionmentioning

confidence: 99%

Combined Extracts of Epimedii Folium and Ligustri Lucidi Fructus with Budesonide Attenuate Airway Remodeling in the Asthmatic Rats by Regulating Apoptosis and Autophagy

Tang

Yingying

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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This study aimed to investigate the effects of the coadministration of budesonide (Bud) and the extracts of Epimedii Folium and Ligustri Lucidi Fructus (EEL) on regulating apoptosis and autophagy in asthmatic rats. Forty Sprague-Dawley rats were divided randomly into five groups (8 rats in each group): normal control (control), asthma model (asthma), Bud (1 mg Bud suspension in 50 ml sterile physiological saline for 30 min), EEL (100 mg/kg EEL), and group of coadministration of Bud and EEL (Bud&EEL, 100 mg/kg EEL plus Bud by nebulized inhalation for 30 min). Rats were sensitized and challenged with ovalbumin for 7 weeks and treated with corresponding drug for 4 weeks. We anesthetized all rats with 25% ethyl carbamate (4 ml/kg) and took lung tissues and BALF after final ovalbumin challenge to observe the lung histopathology and morphometry; apoptosis in BALF and lung tissue; protein expressions of Ki-67, α-SMA, cleaved Caspase-3, p-mTOR, and LC3; and protein and mRNA expressions of Bax, Bcl-2, Caspase-3, P53, mTOR, and Beclin-1. Results showed that Bud&EEL could alleviate airway remodeling, inhibit cell proliferation and autophagy in lung tissue, and promote apoptosis in BALF and lung tissue in ovalbumin-induced asthma rats through downregulating the protein expressions of α-SMA and Ki-67, the protein ratio of LC3-II/LC3-I and Bcl-2/Bax, and the protein and mRNA expressions of Bcl-2 and Beclin-1, while upregulating the protein expressions of cleaved Caspase-3 and p-mTOR, and the protein and mRNA expressions of Bax, Caspase-3, P53, and mTOR. Bud&EEL had better effects than single-use Bud on improving airway remodeling, promoting apoptosis, and regulating the expressions of autophagy- and apoptosis-related proteins. This study suggested that the effects of coadministration of EEL and Bud on regulating apoptosis and autophagy were better than those of single-use Bud treatment, and that might be the mechanism of attenuating airway remodeling, providing an alternative therapy for asthma.

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Increased serum VDBP as a risk predictor for steroid resistance in asthma patients

Abstract: This study provides a novel overview of the difference in serum proteomes of SSA and SRA. We suppose serum VDBP may serve as a useful biomarker for predicting SR in asthma patients, and may participate in the pathogenesis of SRA.

Cited by 18 publications

References 26 publications

Association of vitamin D genetic pathway with asthma susceptibility in the Kurdish population

Association of vitamin D genetic pathway with asthma susceptibility in the Kurdish population

Interleukin‑35 sensitizes monocytes from patients with asthma to glucocorticoid therapy by regulating p38 MAPK

Combined Extracts of Epimedii Folium and Ligustri Lucidi Fructus with Budesonide Attenuate Airway Remodeling in the Asthmatic Rats by Regulating Apoptosis and Autophagy

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