期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：50
页码：E8151-E8158
DOI：10.1073/pnas.1614935113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceWe found that TNF-stimulated gene-6 (TSG6), a secreted 30-kDa immunomodulatory protein, resolved LPS-induced inflammatory lung injury by shifting macrophages from a proinflammatory to an anti-inflammatory phenotype. Macrophages from mice genetically deficient in TSG6 failed to transition, demonstrating the essential role of TSG6 in mediating macrophage plasticity. The finding that TSG6 induced the marked transition in anti-inflammatory macrophages lays the foundation for its therapeutic application. TNF-stimulated gene-6 (TSG6), a 30-kDa protein generated by activated macrophages, modulates inflammation; however, its mechanism of action and role in the activation of macrophages are not fully understood. Here we observed markedly augmented LPS-induced inflammatory lung injury and mortality in TSG6-/- mice compared with WT (TSG6+/+) mice. Treatment of mice with intratracheal instillation of TSG6 prevented LPS-induced lung injury and neutrophil sequestration, and increased survival in mice. We found that TSG6 inhibited the association of TLR4 with MyD88, thereby suppressing NF-{kappa}B activation. TSG6 also prevented the expression of proinflammatory proteins (iNOS, IL-6, TNF, IL-1{beta
