QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 16, Issue 8, 3501-3510, August 2005

This Article Full Text Full Text (PDF) All Versions of this Article: E04-11-1033v1 16/8/3501    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Benus, G. F.J.D. Articles by Eggen, B. J.L. Search for Related Content PubMed PubMed Citation Articles by Benus, G. F.J.D. Articles by Eggen, B. J.L.

Inhibition of the Transforming Growth Factor (TGF) Pathway by Interleukin-1 Is Mediated through TGF-activated Kinase 1 Phosphorylation of SMAD3

Germaine F.J.D. Benus ^* , Albertus T.J. Wierenga  , David J.J. de Gorter ^*, Jan Jacob Schuringa ^*, Ariëtte M. van Bennekum ^*, Loes Drenth-Diephuis ^*, Edo Vellenga , and Bart J.L. Eggen ^*

^* Developmental Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9751 NN Haren, The Netherlands; Department of Hematology, University Hospital Groningen, 9713 GZ Groningen, The Netherlands

Submitted November 30, 2004; Revised May 9, 2005; Accepted May 17, 2005
Monitoring Editor: William Tansey

Transforming growth factor is the prototype of a large family of secreted factors that regulate multiple biological processes. In the immune system, TGF acts as an anti-inflammatory and immunosuppressive molecule, whereas the cytokine interleukin (IL)-1 is a crucial mediator of inflammatory responses and induces proinflammatory genes and acute phase proteins. Here, we present evidence for the existence of a direct inhibitory interaction between the IL-1 and TGF signaling cascades that is not dependent on IL-1–induced SMAD7 expression. IL-1 and its downstream mediator TAK1 inhibit SMAD3-mediated TGF target gene activation, whereas SMAD3 nuclear translocation and DNA binding in response to TGF are not affected. IL-1 transiently induces association between TAK1 and the MAD homology 2 domain of SMAD3, resulting in SMAD3 phosphorylation. Furthermore, IL-1 alleviates the inhibitory effect of TGF on in vitro hematopoietic myeloid colony formation. In conclusion, our data provide evidence for the existence of a direct inhibitory effect of the IL-1-TAK1 pathway on SMAD3-mediated TGF signaling, resulting in reduced TGF target gene activation and restored proliferation of hematopoietic progenitors.

These authors contributed equally to this work.

Address correspondence to: Bart J.L. Eggen (b.j.l.eggen{at}rug.nl).

This article has been cited by other articles:

				J.-H. Zhou, Y.-G. Jiang, R.-W. Wang, S.-Z. Fan, T.-Q. Gong, Q.-Y. Tan, Z. Ma, Y.-P. Zhao, and B. Deng Prevention of stricture development after corrosive esophageal burn with a modified esophageal stent in dogs. J. Thorac. Cardiovasc. Surg., November 1, 2008; 136(5): 1336 - 1342.e7. [Abstract] [Full Text] [PDF]

				T. Lu, L. Tian, Y. Han, M. Vogelbaum, and G. R. Stark Dose-dependent cross-talk between the transforming growth factor-beta and interleukin-1 signaling pathways PNAS, March 13, 2007; 104(11): 4365 - 4370. [Abstract] [Full Text] [PDF]

				A. Behfar, C. Perez-Terzic, R. S. Faustino, D. K. Arrell, D. M. Hodgson, S. Yamada, M. Puceat, N. Niederlander, A. E Alekseev, L. V. Zingman, et al. Cardiopoietic programming of embryonic stem cells for tumor-free heart repair J. Exp. Med., February 19, 2007; 204(2): 405 - 420. [Abstract] [Full Text] [PDF]

				J. L. Jadrich, M. B. O'Connor, and E. Coucouvanis The TGF{beta} activated kinase TAK1 regulates vascular development in vivo. Development, April 1, 2006; 133(8): 1529 - 1541. [Abstract] [Full Text] [PDF]