Menon Mridula P, Hua Kuo-Feng
Department of Biotechnology and Animal Science, National Ilan University, Yilan, Taiwan.
Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Front Immunol. 2020 Sep 25;11:569524. doi: 10.3389/fimmu.2020.569524. eCollection 2020.
The NOD LRR pyrin domain containing protein 3 (NLRP3) inflammasome is a cytosolic multi-proteins conglomerate with intrinsic ATPase activity. Their predominant presence in the immune cells emphasizes its significant role in immune response. The downstream effector proteins IL-1β and IL-18 are responsible for the biological functions of the NLRP3 inflammasome upon encountering the alarmins and microbial ligands. Although the NLRP3 inflammasome is essential for host defense during infections, uncontrolled activation and overproduction of IL-1β and IL-18 increase the risk of developing autoimmune and metabolic disorders. Emerging evidences suggest the action of lncRNAs in regulating the activity of NLRP3 inflammasome in various disease conditions. The long non-coding RNA (lncRNA) is an emerging field of study and evidence on their regulatory role in various diseases is grabbing attention. Recent studies emphasize the functions of lncRNAs in the fine control of the NLRP3 inflammasome at nuclear and cytoplasmic levels by interfering in chromatin architecture, gene transcription and translation. Recently, lncRNAs are also found to control the activity of various regulators of NLRP3 inflammasome. Understanding the precise role of lncRNA in controlling the activity of NLRP3 inflammasome helps us to design targeted therapies for multiple inflammatory diseases. The present review is a novel attempt to consolidate the substantial role of lncRNAs in the regulation of the NLRP3 inflammasome. A deeper insight on the NLRP3 inflammasome regulation by lncRNAs will help in developing targeted and beneficial therapeutics in the future.
含核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎性小体是一种具有内在ATP酶活性的胞质多蛋白聚集体。它们在免疫细胞中的主要存在强调了其在免疫反应中的重要作用。下游效应蛋白白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)在遇到警报素和微生物配体时负责NLRP3炎性小体的生物学功能。尽管NLRP3炎性小体在感染期间对宿主防御至关重要,但IL-1β和IL-18的不受控制的激活和过度产生会增加自身免疫性疾病和代谢紊乱的发生风险。新出现的证据表明长链非编码RNA(lncRNA)在各种疾病状态下调节NLRP3炎性小体活性中的作用。长链非编码RNA是一个新兴的研究领域,关于它们在各种疾病中的调节作用的证据正受到关注。最近的研究强调lncRNA通过干扰染色质结构、基因转录和翻译在核和细胞质水平上对NLRP3炎性小体的精细控制中的功能。最近,还发现lncRNA可控制NLRP3炎性小体的各种调节因子的活性。了解lncRNA在控制NLRP3炎性小体活性中的精确作用有助于我们设计针对多种炎症性疾病的靶向治疗方法。本综述是一次新颖的尝试,旨在巩固lncRNA在调节NLRP3炎性小体中的重要作用。对lncRNA对NLRP3炎性小体调节的更深入了解将有助于在未来开发靶向且有益的治疗方法。