Department of Pharmacology and Toxicology, School of Pharmacy, University of Health and Allied Sciences (UHAS), Ho, Ghana.
Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.
Mediators Inflamm. 2022 Aug 24;2022:2222270. doi: 10.1155/2022/2222270. eCollection 2022.
Airway inflammation in asthma is managed with anti-inflammatory steroids such as dexamethasone (DEX). However, about 20% of asthmatics do not respond to this therapy and are classified as steroid-resistant. Currently, no effective therapy is available for steroid-resistant asthma. This work therefore evaluated the effect of a plant sterol, stigmasterol (STIG), and stigmasterol-dexamethasone combination (STIG+DEX) in LPS-ovalbumin-induced steroid-resistant asthma in Guinea pigs. To do this, the effect of drugs on inflammatory features such as airway hyperreactivity and histopathology of lung tissue was evaluated. Additionally, the possible pathway of drug action was assessed by measuring events such neutrophil levels, oxidative and nitrative stress, and histone deacetylase 2 (HDAC2) and interleukin 17 (IL-17) levels. STIG alone did not affect inflammatory features, although it caused some changes in the molecular events associated with steroid-resistant asthma. However, STIG+DEX caused significant modulation of inflammatory features by protecting against destruction of lung tissue. The modulation of inflammatory features was associated with significant inhibition of neutrophilia and oxidative and nitrative stress, decrease in HDAC2, and increase in IL-17 levels that are usually associated with steroid-resistant asthma. Our findings show that although STIG and DEX individually do not protect against steroid-resistant asthma, their coadministration results in significant modulation of inflammatory features and the associated molecular events that lead to steroid-resistant asthma.
气道炎症在哮喘中通过使用抗炎类固醇来控制，如地塞米松（DEX）。然而，大约 20%的哮喘患者对这种治疗方法没有反应，被归类为类固醇耐药。目前，对于类固醇耐药性哮喘还没有有效的治疗方法。因此，这项工作评估了植物固醇麦角固醇（STIG）和麦角固醇-地塞米松联合（STIG+DEX）在 LPS-卵清蛋白诱导的豚鼠类固醇耐药性哮喘中的作用。为此，评估了药物对气道高反应性和肺组织组织病理学等炎症特征的影响。此外，通过测量中性粒细胞水平、氧化和硝化应激以及组蛋白去乙酰化酶 2（HDAC2）和白细胞介素 17（IL-17）水平等事件，评估了药物作用的可能途径。单独的 STIG 没有影响炎症特征，尽管它对与类固醇耐药性哮喘相关的分子事件产生了一些变化。然而，STIG+DEX 通过保护肺组织免受破坏，对炎症特征产生了显著的调节作用。炎症特征的调节与中性粒细胞增多和氧化、硝化应激的显著抑制、HDAC2 的减少以及通常与类固醇耐药性哮喘相关的 IL-17 水平的增加有关。我们的研究结果表明，尽管 STIG 和 DEX 单独使用不能预防类固醇耐药性哮喘，但它们的联合使用可显著调节炎症特征和相关的分子事件，从而导致类固醇耐药性哮喘。
