Department of Translational Research, Western University of Health Sciences, Pomona, CA 91766, USA.
Department of Orthopedic Surgery, Creighton University School of Medicine, Omaha, NE 68178, USA.
Int J Environ Res Public Health. 2022 May 7;19(9):5690. doi: 10.3390/ijerph19095690.
Osteoarthritis (OA) is a chronic inflammatory disease where pro-inflammatory cytokines, damage-associated molecular patterns (DAMPs), and macrophages play a crucial role. However, the interactive role of these mediators, the exact cause precipitating OA and definitive treatment for OA are not known yet. Moreover, the interactive role of interleukin (IL)-33 and IL-37 with other factors in the pathogenesis of OA has not been discussed elaborately. In this study, we analyzed the expression of IL-33 and IL-37 in human OA knee and hip joint cartilage tissues. The effect of increased DAMPs, IL-33, and IL-37 on IL-6, tumor necrosis factor (TNF)-α, toll-like receptors (TLRs), and matrix metalloproteinases (MMPs) expression was delineated using human normal and osteoarthritic chondrocytes. The effect of anti-inflammatory cytokine IL-37 on various mediators of inflammation in the presence of IL-33, rHMGB-1, and LPS was investigated to delineate the effects of IL-37. Further, the effects of blocking IL-33 downstream signaling and the effects of IL-33 and IL-37 on macrophage polarization were assessed along with examining the macrophage phenotypes in human OA cartilage tissues. The results of this study revealed increased expression of IL-33 in OA cartilage and that IL-33 increases IL-6, TNF-α, TLRs, and MMPs expression and favors phenotypic conversion towards the M1 phenotype, while IL-37 and blocking IL-33 receptor ST2 have opposite effects. Overall, the results suggest that blocking IL-33 and increasing IL-37 act synergistically to attenuate inflammation and might serve as potential therapeutics in OA.
骨关节炎（OA）是一种慢性炎症性疾病，其中促炎细胞因子、损伤相关分子模式（DAMPs）和巨噬细胞发挥着关键作用。然而，这些介质的相互作用、引发 OA 的确切原因以及 OA 的明确治疗方法尚不清楚。此外，白细胞介素（IL）-33 和 IL-37 与 OA 发病机制中其他因素的相互作用尚未详细讨论。在这项研究中，我们分析了 IL-33 和 IL-37 在人类 OA 膝关节和髋关节软骨组织中的表达。使用人正常和骨关节炎软骨细胞，阐述了 DAMPs、IL-33 和 IL-37 增加对 IL-6、肿瘤坏死因子（TNF）-α、Toll 样受体（TLRs）和基质金属蛋白酶（MMPs）表达的影响。研究了抗炎细胞因子 IL-37 在存在 IL-33、rHMGB-1 和 LPS 时对各种炎症介质的影响，以阐明 IL-37 的作用。此外，还评估了阻断 IL-33 下游信号和 IL-33 和 IL-37 对巨噬细胞极化的影响，同时检查了人 OA 软骨组织中的巨噬细胞表型。这项研究的结果表明，OA 软骨中 IL-33 的表达增加，IL-33 增加了 IL-6、TNF-α、TLRs 和 MMPs 的表达，并有利于向 M1 表型的表型转化，而 IL-37 和阻断 IL-33 受体 ST2 则具有相反的作用。总的来说，这些结果表明，阻断 IL-33 和增加 IL-37 协同作用以减轻炎症，可能成为 OA 的潜在治疗方法。
