Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center, Kazan, Russian Federation.
Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation.
Curr Pharm Des. 2018;24(20):2236-2240. doi: 10.2174/1381612824666180716170128.
The development of an effective system for the treatment of inflammatory diseases requires comprehensive studies of the cellular signaling molecular networks comprising responses to various stressors, including pathogenic and non-pathogenic microorganisms. Significant attention on fundamental and applied research has recently focused on inducers of hemе oxygenase-1 (HO-1) and inhibitors of the expression of this enzyme, which regulates expression of this and other cytoprotective molecules and modulation of inflammation. Recent studies indicate that mycoplasmas (a major group of human pathogens of the Mollicutes) are capable of modulating inflammatory responses through the activation of the Nrf2 and the expression of HO-1. In vitro experiments demonstrate that the membrane lipoproteins (LAMPs), along with lipoprotein derivatives (lipopeptide MALP-2) in mycoplasmas cause a "cross-talk" between the pro- and antiinflammatory signaling pathways. Importantly, lipopeptide/lipoprotein - induced expression of HO-1 tends to suppress inflammation.
The study of the molecular network that causes the corresponding outcome can facilitate the development of new approaches for the treatment of inflammatory processes. The derivatives of LAMPs and MALP-2 and of their analogues may prove promising for the treatment of diseases associated with chronic inflammation.
为了开发有效的炎症性疾病治疗系统,需要全面研究包含对各种应激源(包括致病和非致病微生物)反应的细胞信号分子网络。最近,基础研究和应用研究都高度关注血红素加氧酶-1(HO-1)的诱导剂和该酶表达的抑制剂,因为它们可以调节该酶和其他细胞保护分子的表达,并调节炎症。最近的研究表明,支原体(柔膜体纲的一大类人类病原体)能够通过激活 Nrf2 和表达 HO-1 来调节炎症反应。体外实验表明,支原体中的膜脂蛋白(LAMPs)以及脂蛋白衍生物(脂肽 MALP-2)在促炎和抗炎信号通路之间引起“串扰”。重要的是,脂肽/脂蛋白诱导的 HO-1 表达往往会抑制炎症。
研究导致相应结果的分子网络可以促进治疗炎症过程的新方法的发展。LAMPs 和 MALP-2 的衍生物及其类似物可能有望用于治疗与慢性炎症相关的疾病。