期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 41, 页码 16239-16244出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0705971104
关键词
lipopolysaccharide; cytokines; Toll-like receptor; MyD88; innate immunity
Activin A is a member of the transforming growth factor-beta superfamily, which we have identified as having a role in inflammatory responses. We show that circulating levels of activin increase rapidly after LPS-induced challenge through activation of Toll-like receptor 4 and the key adaptor protein, MyD88. Treatment with the activin-binding protein, follistatin, alters the profiles of TNF, IL-1 beta, and IL-6 after LPS stimulation, indicating that activin modulates the release of several key proinflammatory cytokines. Further, mice administered one 10-mu g dose of follistatin to block activin effects have increased survival after a lethal dose of LIPS, and the circulating levels of activin correlate with survival outcome. These findings demonstrate activin A's crucial role in the inflammatory response and show that blocking its actions by the use of follistatin has significant therapeutic potential to reduce the severity of inflammatory diseases.
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