前胶原肽酶
治疗效果
发病机制
免疫印迹
医学
下调和上调
癌症研究
MAPK/ERK通路
实时聚合酶链反应
刺激
受体
甲状腺
格雷夫斯病
透明质酸
内分泌学
污渍
免疫学
肌成纤维细胞
信使核糖核酸
信号转导
促甲状腺激素受体
内科学
封锁
车站3
细胞生长
病理
分子生物学
细胞
效应器
Graves眼病
p38丝裂原活化蛋白激酶
成纤维细胞
细胞外
病态的
免疫系统
化学
作者
Hee Joo Yoon,Hyun Young Park,J. Kim,Soo Hyun Choi,Don O. Kikkawa,James S. Swaney,David J. King,Yasmin M. Vasquez,Jin Sook Yoon
摘要
Thyroid eye disease (TED), a major extrathyroidal manifestation of Graves' disease, is driven by the underlying autoimmune responses. This study aimed to elucidate the pathological role of IL-11 in TED and evaluate the therapeutic potential of LASN01, a potent, fully human antibody that targets IL-11 receptor alpha (IL-11Rα). IL-11 (P < 0.001) and IL-11Rα (P = 0.003) mRNA were significantly elevated in TED orbital tissues (n = 15) compared to normal controls (n = 15) by quantitative real-time polymerase chain reaction (RT-qPCR). IL-11 expressions in both TED and normal orbital fibroblasts (OFs) were upregulated after treatment with either transforming growth factor-beta (TGF-β) or insulin-like growth factor 1 (IGF-1). Furthermore, IL-11 exerted a synergistic stimulatory effect on hyaluronan production in TED OFs when combined with either TGF-β (3.21-fold, P < 0.001) or IGF-1 (2.83-fold, P < 0.001). Notably, the combination of IL-11 and TGF-β induced greater procollagen production (6.17-fold, P < 0.001). Blocking IL-11R with LASN01 effectively reduced both hyaluronan (94% reduction, P < 0.001) and procollagen production (36% reduction, P = 0.002) in ELISA under various stimulation conditions. Finally, Western blot analysis showed that LASN01 blocked STAT3 and ERK phosphorylation in TED OFs, which are known as downstream effectors of IL-11 signaling. This study systematically analyzed how IGF-1 and TGF-β promote IL-11 expression in OFs and examined the downstream effects of IL-11 on hyaluronan and procollagen production, highlighting the central role of IL-11 in TED-associated tissue expansion and fibrosis. The inhibitory effects of LASN01 on hyaluronan and procollagen production suggest that targeting IL-11R could represent an effective therapeutic option for TED, providing a foundation for future clinical applications.
科研通智能强力驱动
Strongly Powered by AbleSci AI