| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Institutes of
*
Chemistry and Biochemistry and
Genetics and General Biology, University of Salzburg, Salzburg, Austria
Proteins of the suppressors of cytokine signaling (SOCS) family have important functions as negative regulators of cytokine signaling. We show here that SOCS-1 expression can be induced in the human epithelial lung cell line A549 by IL-4 and IL-13. Analysis of reporter gene constructs under control of the SOCS-1 promoter provides evidence that IL-4- and IL-13-induced up-regulation is dependent on three IFN-
-activated sequence motifs of the sequence TTC(N)4GAA, which is known for binding STAT6. The three motifs are situated close to each other 
600 bp upstream of the transcriptional initiation site. When mutations were inserted into all three IFN--activated sequence motifs at the same time, IL-4-IL-13-induced luciferase activity was abrogated. With single and double mutants, promoter activity was diminished in comparison with the wild-type promoter. STAT6 is therefore required for IL-4-IL-13-dependent SOCS-1 expression in A549 cells, and the three identified binding motifs cooperate to induce maximal transcription. EMSAs conducted with nuclear extracts of IL-4- and IL-13-stimulated A549 cells showed that STAT6 was able to bind to each of the three binding motifs. Finally, cotransfection of a SOCS-1 expression vector inhibited activation of SOCS-1 promoter luciferase constructs. Thus, SOCS-1 is able to autoregulate its expression via a negative feedback loop.
This article has been cited by other articles:
|
|
 |
|
  M. L. Slattery and F.A. Fitzpatrick Convergence of Hormones, Inflammation, and Energy-Related Factors: A Novel Pathway of Cancer Etiology Cancer Prevention Research, November 1, 2009; 2(11): 922 - 930. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fukuyama, T. Nakano, T. Matsumoto, B. G. G. Oliver, J. K. Burgess, A. Moriwaki, K. Tanaka, M. Kubo, T. Hoshino, H. Tanaka, et al. Pulmonary Suppressor of Cytokine Signaling-1 Induced by IL-13 Regulates Allergic Asthma Phenotype Am. J. Respir. Crit. Care Med., June 1, 2009; 179(11): 992 - 998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kenth, J. A M. Mergelas, and C. G. Goodyer Developmental changes in the human GH receptor and its signal transduction pathways J. Endocrinol., July 1, 2008; 198(1): 71 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mottok, C. Renne, K. Willenbrock, M.-L. Hansmann, and A. Brauninger Somatic hypermutation of SOCS1 in lymphocyte-predominant Hodgkin lymphoma is accompanied by high JAK2 expression and activation of STAT6 Blood, November 1, 2007; 110(9): 3387 - 3390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Monick, L. S. Powers, I. Hassan, D. Groskreutz, T. O. Yarovinsky, C. W. Barrett, E. M. Castilow, D. Tifrea, S. M. Varga, and G. W. Hunninghake Respiratory Syncytial Virus Synergizes with Th2 Cytokines to Induce Optimal Levels of TARC/CCL17 J. Immunol., August 1, 2007; 179(3): 1648 - 1658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Albanesi, H. R. Fairchild, S. Madonna, C. Scarponi, O. De Pita, D. Y. M. Leung, and M. D. Howell IL-4 and IL-13 Negatively Regulate TNF-{alpha}- and IFN-{gamma}-Induced beta-Defensin Expression through STAT-6, Suppressor of Cytokine Signaling (SOCS)-1, and SOCS-3 J. Immunol., July 15, 2007; 179(2): 984 - 992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Ingram, A. Antao-Menezes, J. B. Mangum, O. Lyght, P. J. Lee, J. A. Elias, and J. C. Bonner Opposing Actions of Stat1 and Stat6 on IL-13-Induced Up-Regulation of Early Growth Response-1 and Platelet-Derived Growth Factor Ligands in Pulmonary Fibroblasts J. Immunol., September 15, 2006; 177(6): 4141 - 4148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Qin, C. A. Wilson, S. J. Lee, and E. N. Benveniste IFN-{beta}-induced SOCS-1 negatively regulates CD40 gene expression in macrophages and microglia FASEB J, May 1, 2006; 20(7): 985 - 987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. O. Abonyo, M. S. Alexander, and A. S. Heiman Autoregulation of CCL26 synthesis and secretion in A549 cells: a possible mechanism by which alveolar epithelial cells modulate airway inflammation Am J Physiol Lung Cell Mol Physiol, September 1, 2005; 289(3): L478 - L488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Scotton, F. O. Martinez, M. J. Smelt, M. Sironi, M. Locati, A. Mantovani, and S. Sozzani Transcriptional Profiling Reveals Complex Regulation of the Monocyte IL-1{beta} System by IL-13 J. Immunol., January 15, 2005; 174(2): 834 - 845. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Fulkerson, N. Zimmermann, L. M. Hassman, F. D. Finkelman, and M. E. Rothenberg Pulmonary Chemokine Expression Is Coordinately Regulated by STAT1, STAT6, and IFN-{gamma} J. Immunol., December 15, 2004; 173(12): 7565 - 7574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Heller, S. Matsukura, S. N. Georas, M. R. Boothby, P. B. Rothman, C. Stellato, and R. P. Schleimer Interferon-{gamma} Inhibits STAT6 Signal Transduction and Gene Expression in Human Airway Epithelial Cells Am. J. Respir. Cell Mol. Biol., November 1, 2004; 31(5): 573 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Travagli, M. Letourneur, J. Bertoglio, and J. Pierre STAT6 and Ets-1 Form a Stable Complex That Modulates Socs-1 Expression by Interleukin-4 in Keratinocytes J. Biol. Chem., August 20, 2004; 279(34): 35183 - 35192. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
