https://scholars.lib.ntu.edu.tw/handle/123456789/637984
標題: | Integrin αv and Vitronectin Prime Macrophage-Related Inflammation and Contribute the Development of Dry Eye Disease | 作者: | Ho, Tsung-Chuan Yeh, Shu-I SHOW-LI CHEN Tsao, Yeou-Ping |
關鍵字: | c(RGDfK); dry eye disease; inflammation; macrophage; vitronectin; αv integrin | 公開日期: | 5-八月-2021 | 卷: | 22 | 期: | 16 | 來源出版物: | International journal of molecular sciences | 摘要: | Cell signaling mediated by the αv integrin plays a pivotal role in macrophage activation in various inflammatory processes, but its involvement in the pathogenesis of dry eye disease (DED) remains unclear. In a murine model of DED, we found increased αv integrin expression in ocular surface macrophages. The αv integrins inhibitor c(RGDfK) ameliorated the corneal damage caused by DED, suggesting a pathogenic role for αv integrin. Because tear hyperosmolarity induces ocular inflammation in DED, a hyperosmolar culture of murine bone marrow-derived macrophages (BMDMs) is used to reproduce inflammation in vitro. However, the expression of proinflammatory cytokine mRNA was minimal, even though αv integrin was induced. In searching for components that are involved in αv integrin-mediated inflammation but that are missing from the culture model, we showed that the levels of vitronectin (VTN), a binding ligand of αv integrins, were increased in the tear fluid and conjunctival stroma of DED animals. The addition of VTN prominently enhanced hyperosmolarity-induced inflammation in BMDMs. Mechanistically, we showed that VTN/αv integrins mediated NF-κB activation to induce inflammatory gene expression in the BMDMs. Our findings indicate that interaction the of VTN with αv integrins is a crucial step in the inflammatory process in DED and suggests a novel therapeutic target. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/637984 | ISSN: | 16616596 | DOI: | 10.3390/ijms22168410 |
顯示於: | 微生物學科所 |
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