Park Jun-Young, Kwon Song, Kim Sang-Hyun, Kang Youn Joo, Khang Dongwoo
Department of Gachon Advanced Institute for Health Science & Technology (GAIHST), Gachon University, Incheon 21999, South Korea.
Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, South Korea.
ACS Appl Mater Interfaces. 2020 Sep 2;12(35):38936-38949. doi: 10.1021/acsami.0c09842. Epub 2020 Aug 24.
Understanding the crosstalk between synoviocytes and macrophages is very important for the development of strategies to regulate inflammatory responses in an inflamed synovium. Simultaneous regulation of the pro- and anti-inflammatory responses of synoviocytes and macrophages (repolarization) is critical for the treatment of arthritis. Thus, the immune regulatory functions of an ideal nanodrug should not only decrease the pro-inflammatory response but also effectively increase the anti-inflammatory response. In this study, crosstalk between synoviocytes and macrophages was found to be significantly involved in the activation and deactivation of inflammatory responses in the synovium. Interestingly, a developed triamcinolone-gold nanoparticle (Triam-AuNP) complex both decreased the pro-inflammatory responses and increased the anti-inflammatory responses of fibroblast-like synoviocytes (FLSs) and macrophages via repolarization of macrophages from the M1 to the M2 phenotype. In contrast, triamcinolone alone only decreased the pro-inflammatory responses of FLSs and macrophages without upregulating their anti-inflammatory responses. In vitro (human), ex vivo (human), and in vivo (mouse) analyses clearly indicated that Triam-AuNPs effectively regulated the expression of both pro- and anti-inflammatory cytokines in FLSs and effectively repolarized activity of macrophages in the inflamed synovium. Furthermore, Triam-AuNPs significantly promoted cartilage regeneration, whereas triamcinolone alone did not induce either FLS anti-inflammatory activity or macrophage repolarization.
了解滑膜细胞与巨噬细胞之间的相互作用对于制定调节炎症滑膜中炎症反应的策略非常重要。同时调节滑膜细胞和巨噬细胞的促炎和抗炎反应（再极化）对于关节炎的治疗至关重要。因此，理想纳米药物的免疫调节功能不仅应降低促炎反应，还应有效增强抗炎反应。在本研究中，发现滑膜细胞与巨噬细胞之间的相互作用在滑膜炎症反应的激活和失活中起重要作用。有趣的是，一种已开发的曲安奈德-金纳米颗粒（Triam-AuNP）复合物通过将巨噬细胞从M1表型重极化到M2表型，既降低了促炎反应，又增强了成纤维样滑膜细胞（FLS）和巨噬细胞的抗炎反应。相比之下，单独使用曲安奈德仅降低了FLS和巨噬细胞的促炎反应，而未上调其抗炎反应。体外（人）、离体（人）和体内（小鼠）分析清楚地表明，Triam-AuNPs有效调节了FLS中促炎和抗炎细胞因子的表达，并有效重极化了炎症滑膜中巨噬细胞的活性。此外，Triam-AuNPs显著促进了软骨再生，而单独使用曲安奈德既未诱导FLS的抗炎活性，也未诱导巨噬细胞的重极化。
