Ouyang Lihuan, Su Guomei, Quan Jingyun, Xiong Zhilin, Lai Tianwen
Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China.
Chin Med J Pulm Crit Care Med. 2023 Jun 3;1(2):108-112. doi: 10.1016/j.pccm.2023.04.003. eCollection 2023 Jun.
Steroid resistance represents a major clinical problem in the treatment of severe asthma, and therefore a better understanding of its pathogenesis is warranted. Recent studies indicated that histone deacetylase 2 (HDAC2) and interleukin 17A (IL-17A) play important roles in severe asthma. HDAC2 activity is reduced in patients with severe asthma and smoking-induced asthma, perhaps accounting for the amplified expression of inflammatory genes, which is associated with increased acetylation of glucocorticoid receptors. Neutrophilic inflammation contributes to severe asthma and may be related to T helper (Th) 17 rather than Th2 cytokines. IL-17A levels are elevated in severe asthma and correlate with the presence of neutrophils. Restoring the activity of HDAC2 or targeting the Th17 signaling pathway is a potential therapeutic approach to reverse steroid insensitivity.
激素抵抗是重症哮喘治疗中的一个主要临床问题，因此有必要更好地了解其发病机制。最近的研究表明，组蛋白去乙酰化酶2（HDAC2）和白细胞介素17A（IL-17A）在重症哮喘中起重要作用。重症哮喘患者和吸烟诱导的哮喘患者中HDAC2活性降低，这可能是炎症基因表达增强的原因，而炎症基因表达增强与糖皮质激素受体乙酰化增加有关。中性粒细胞炎症导致重症哮喘，可能与辅助性T（Th）17细胞而非Th2细胞因子有关。重症哮喘中IL-17A水平升高，且与中性粒细胞的存在相关。恢复HDAC2的活性或靶向Th17信号通路是逆转激素不敏感性的一种潜在治疗方法。
