DOI: 10.1073/pnas.0705971104. Activin A is a critical component of the inflammatory response, and its binding protein, follistatin, reduces mortality in endotoxemia

Activin A is a critical component of the inflammatory response, and its binding protein, follistatin, reduces mortality in endotoxemia

10.1073/pnas.0705971104

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Activin A is a member of the transforming growth factor-β 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-1β, and IL-6 after LPS stimulation, indicating that activin modulates the release of several key proinflammatory cytokines. Further, mice administered one 10-μg dose of follistatin to block activin effects have increased survival after a lethal dose of LPS, 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.

Bibliography

Jones, K. L., Mansell, A., Patella, S., Scott, B. J., Hedger, M. P., de Kretser, D. M., & Phillips, D. J. (2007). Activin A is a critical component of the inflammatory response, and its binding protein, follistatin, reduces mortality in endotoxemia. Proceedings of the National Academy of Sciences, 104(41), 16239â16244.

Authors 7

Kristian L. Jones (first)
Ashley Mansell (additional)
Shane Patella (additional)
Bernadette J. Scott (additional)
Mark P. Hedger (additional)
David M. de Kretser (additional)
David J. Phillips (additional)

References 36 Referenced 236

10.1016/S0952-7915(99)80004-1
10.1038/90609
DJ Phillips The Cytokine Handbook, eds A Thomson, MT Lotze (Academic, 4th Ed, London) Vol 2, 1153–1177 (2003). (10.1016/B978-012689663-3/50054-5) / The Cytokine Handbook by Phillips DJ (2003)
10.1006/frne.1998.0169
G Hübner, M Brauchle, M Gregor, S Werner Lab Invest 77, 311–318 (1997). / Lab Invest by Hübner G (1997)
10.1530/eje.0.1480559
10.1046/j.1365-2249.1998.00522.x
10.4049/jimmunol.165.2.618
10.1126/science.282.5396.2085
10.1084/jem.189.4.615
10.1016/S1074-7613(00)80596-8
10.4049/jimmunol.177.10.7122
10.1074/jbc.M301742200
10.1016/0006-291X(87)90430-X
10.1046/j.1471-4159.2003.01834.x
10.1210/endo.141.5.7531
10.1677/joe.0.1820069
10.1053/j.gastro.2004.11.063
10.1038/sj.bjp.0702626
10.1073/pnas.91.19.8817
KA Coerver, TK Woodruff, MJ Finegold, J Mather, A Bradley, MM Matzuk Mol Endocrinol 10, 534–543 (1996). / Mol Endocrinol by Coerver KA (1996)
10.1038/374354a0
10.1002/jcp.1113
10.1002/jcb.10613
10.1111/j.1365-2249.1993.tb06003.x
10.1089/jir.1998.18.491
10.1159/000084848
10.1006/cyto.1999.0597
10.1053/plac.1999.0451
10.1096/fj.02-1211fje
10.1038/nsb1103-874
10.1016/j.mce.2006.03.041
10.1084/jem.176.5.1449
10.1074/jbc.C400289200
10.1677/joe.0.1480267
10.1093/humrep/14.3.827

Dates

Type	When
Created	17 years, 10 months ago (Oct. 2, 2007, 8:25 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 4:34 p.m.)
Indexed	2 months ago (June 26, 2025, 11:44 a.m.)
Issued	17 years, 10 months ago (Oct. 9, 2007)
Published	17 years, 10 months ago (Oct. 9, 2007)
Published Online	17 years, 10 months ago (Oct. 9, 2007)
Published Print	17 years, 10 months ago (Oct. 9, 2007)

Funders 0

None

BibTeX

@article{Jones_2007, title={Activin A is a critical component of the inflammatory response, and its binding protein, follistatin, reduces mortality in endotoxemia}, volume={104}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0705971104}, DOI={10.1073/pnas.0705971104}, number={41}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Jones, Kristian L. and Mansell, Ashley and Patella, Shane and Scott, Bernadette J. and Hedger, Mark P. and de Kretser, David M. and Phillips, David J.}, year={2007}, month=oct, pages={16239–16244} }

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