Pilot Study of the ex vivo Blood Leukocytes’ Proteomic Response to Prednisone Stimulation in Corticosteroid-responsive Asthma

IF 0.5 4区生物学 Q4 BIOCHEMICAL RESEARCH METHODS

Current Proteomics Pub Date : 2023-02-20 DOI:10.2174/1570164620666230220112500

A. Nikolić, Kevin J. Mark, S. Dragicevic, T. Babic, K. Milosevic, B. Nestorović, V. Beškoski

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Abstract

Leukocytes are key cellular effectors of inflammation in asthma and understanding their function in this disease is of crucial importance. Blood leukocytes reflect the actions of their counterparts in the lungs and they can be obtained through minimal invasive procedures as part of the peripheral blood. Leukocytes are key cellular effectors of inflammation in asthma and understanding their function in this disease is of crucial importance. Blood leukocytes reflect the actions of their counterparts in the lungs and they can be obtained through minimal invasive procedure as part of the peripheral blood. The aim of the study was to identify proteins in blood leukocyte proteomes that respond to ex vivo treatment by prednisone in order to pinpoint candidates for predictive biomarkers in corticosteroid-responsive asthma. The study included five children diagnosed with asthma and five healthy children. After the ex vivo treatment of blood samples with prednisone, lysis of erythrocytes was performed and proteins were extracted from the remaining leukocytes by ultrasonic disintegration. Protein extracts were analyzed by reversed phase nano-liquidchromatography–tandem mass spectrometry (LC–MS/MS). The stimulation of asthmatics' leukocytes with prednisone has led to an increase in the levels of FYB (fold change 3.4) and LYZ (fold change 2.2) with a statistical significance of p<0.005. The two proteins with expressions significantly altered upon the prednisone treatment should be further explored as tools to evaluate the patient's response before therapy administration, especially when lung function measurements are not possible, as is the case with young pediatric patients. The approach that entails ex vivo response of blood leukocytes to therapeutics can facilitate asthma management and help overcome the need for therapeutic adjustments in a clinical setting. /

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皮质类固醇反应性哮喘患者体内血液白细胞对强的松刺激的蛋白质组反应的初步研究

白细胞是哮喘炎症的关键细胞效应器，了解它们在哮喘中的功能至关重要。血液中的白细胞反映了它们在肺中的对应物的活动，它们可以通过微创手术作为外周血的一部分获得。白细胞是哮喘炎症的关键细胞效应器，了解它们在哮喘中的功能至关重要。血液中的白细胞反映了它们在肺中的对应物的活动，它们可以通过微创手术作为外周血的一部分获得。该研究的目的是鉴定血液白细胞蛋白质组中对泼尼松体外治疗有反应的蛋白质，以确定皮质类固醇反应性哮喘预测生物标志物的候选物。该研究包括5名被诊断患有哮喘的儿童和5名健康儿童。经强的松体外处理后的血液样本，进行红细胞的溶解，并从剩余的白细胞中提取蛋白质超声解体。采用反相纳米液相色谱-串联质谱法(LC-MS /MS)对蛋白质提取物进行分析。强的松刺激哮喘患者白细胞导致FYB (fold change 3.4)、LYZ (fold change 2.2)水平升高，差异有统计学意义p<0.005。这两种蛋白在强的松治疗后表达显著改变，应进一步探索作为治疗前评估患者反应的工具，特别是在不可能进行肺功能测量的情况下，如年轻儿科患者。这种方法需要血液白细胞对治疗药物的体外反应，可以促进哮喘管理，并有助于克服临床环境中治疗调整的需要

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来源期刊

Current Proteomics BIOCHEMICAL RESEARCH METHODS-BIOCHEMISTRY & MOLECULAR BIOLOGY

CiteScore

1.60

自引率

0.00%

发文量

审稿时长

>0 weeks

期刊介绍： Research in the emerging field of proteomics is growing at an extremely rapid rate. The principal aim of Current Proteomics is to publish well-timed in-depth/mini review articles in this fast-expanding area on topics relevant and significant to the development of proteomics. Current Proteomics is an essential journal for everyone involved in proteomics and related fields in both academia and industry. Current Proteomics publishes in-depth/mini review articles in all aspects of the fast-expanding field of proteomics. All areas of proteomics are covered together with the methodology, software, databases, technological advances and applications of proteomics, including functional proteomics. Diverse technologies covered include but are not limited to: Protein separation and characterization techniques 2-D gel electrophoresis and image analysis Techniques for protein expression profiling including mass spectrometry-based methods and algorithms for correlative database searching Determination of co-translational and post- translational modification of proteins Protein/peptide microarrays Biomolecular interaction analysis Analysis of protein complexes Yeast two-hybrid projects Protein-protein interaction (protein interactome) pathways and cell signaling networks Systems biology Proteome informatics (bioinformatics) Knowledge integration and management tools High-throughput protein structural studies (using mass spectrometry, nuclear magnetic resonance and X-ray crystallography) High-throughput computational methods for protein 3-D structure as well as function determination Robotics, nanotechnology, and microfluidics.