Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D׳Alcontres, 31-98166 Messina, Italy.
Biomolecules. 2021 Feb 25;11(3):352. doi: 10.3390/biom11030352.
Osteoarthritis (OA) is one of the most common and widespread diseases which is highly disabling for humans. This makes OA a chronic disease for which it is urgent to find new therapeutic strategies. The inflammatory state in OA contributes to its progression through multiple mechanisms involving the recruitment of phagocytes and leukocytes, inflammatory response, and reactive oxygen species (ROS) production. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) is classifiable as a piperidine nitroxide, with excellent antioxidant effects, while its anti-inflammatory role is not yet clear. On this basis, we explored its promising biological properties in two in vitro model:, macrophage (J774) and chondrocyte (CC) cell lines. With this aim in mind, we induced inflammation in J774 and CC using lipopolysaccharide (LPS) and Interleukin1β (IL-1β), and after 24, 72 and 168 h of tempol treatment analyzed their effects on cytotoxicity and anti-inflammatory activity. Our data suggested that tempol treatment is able to reduce inflammation and nitrite production in LPS-induced J774 as well as reducing the production of proinflammatory mediators including cytokines, enzymes, and metalloproteases (MMPs) in IL-1β-stimulated CC. Thus, since inflammation and oxidative stress have a crucial role in the pathogenesis and progression of OA, tempol could be considered as a new therapeutic approach for this pathology.
骨关节炎(OA)是一种最常见和广泛的疾病,对人类的致残率很高。这使得 OA 成为一种慢性疾病,迫切需要寻找新的治疗策略。OA 中的炎症状态通过涉及吞噬细胞和白细胞募集、炎症反应和活性氧(ROS)产生的多种机制促进其进展。Tempol(4-羟基-2,2,6,6-四甲基哌啶-1-氧自由基)可归类为哌啶氮氧化物,具有出色的抗氧化作用,但其抗炎作用尚不清楚。在此基础上,我们在两种体外模型中探索了其有前途的生物学特性:巨噬细胞(J774)和软骨细胞(CC)细胞系。基于此目的,我们使用脂多糖(LPS)和白细胞介素 1β(IL-1β)诱导 J774 和 CC 炎症,然后在 tempol 处理 24、72 和 168 小时后分析其对细胞毒性和抗炎活性的影响。我们的数据表明,Tempol 处理能够降低 LPS 诱导的 J774 中的炎症和亚硝酸盐产生,以及降低 IL-1β刺激的 CC 中促炎介质包括细胞因子、酶和金属蛋白酶(MMPs)的产生。因此,由于炎症和氧化应激在 OA 的发病机制和进展中起着至关重要的作用,Tempol 可以被认为是这种病理学的一种新的治疗方法。