International Immunology Advance Access originally published online on March 22, 2007
International Immunology 2007 19(5):609-619; doi:10.1093/intimm/dxm026
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
An RNA-binding protein 
CP-1 is involved in the STAT3-mediated suppression of NF-
B transcriptional activity
1 Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
2 Department of Hematology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
Correspondence to: T. Kobayashi; E-mail: takashik{at}bioreg.kyushu-u.ac.jp
Signal transducer and activator of transcription 3 (STAT3) has been shown to mediate the anti-inflammatory effect of IL-10. Activated STAT3 suppresses LPS-induced IL-6, tumor necrosis factor-
and IL-12 gene expression in macrophages and dendritic cells. However, the mechanism of Toll-like receptor (TLR) signal suppression by STAT3 has not been clarified. In this study, we investigated the effect of constitutively activated STAT3 (STAT3C) on LPS-induced nuclear factor-
B (NF-B) activation. The forced expression of STAT3C in HEK293/TLR4 cells, but neither wild-type STAT3 nor dominant-negative form of STAT3, suppressed LPS–TLR4-mediated NF-B reporter activation. The over-expression of STAT3C did not affect the signal transduction of TLR4, such as the phosphorylation of inhibitory nuclear factor-B and mitogen-activated protein kinases and the DNA-binding activity of NF-B. Thus, STAT3C could suppress the transcriptional and/or translational activity of NF-B. To define the molecular mechanism, we searched STAT3C-binding proteins by using a proteomic approach and found that a novel RNA-binding protein, CP-1, interacted with STAT3C. CP-1 is a K-homology domain-containing RNA-binding protein with specificity for C-rich pyrimidine tracts. Such proteins play pivotal roles in a broad-spectrum of transcriptional and translational events. The over-expression of CP-1 augmented the suppressive effect of STAT3C on NF-B activation in HEK293/TLR4 cells. Furthermore, the forced expression of CP-1 enhanced the antagonistic effect of IL-10 on IL-6 production in RAW264.7 cells, while small interfering RNA against CP-1 reduced it. These data suggest that CP-1 is involved in the STAT3-mediated suppression of NF-B activity.
Keywords: gene regulation, IL-10, lipopolysaccharide, NF-B, signal transduction, STAT3, Toll-like receptor 4
Transmitting editor: T. Watanabe
Received 4 January 2007, accepted 15 February 2007.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. Kozela, M. Pietr, A. Juknat, N. Rimmerman, R. Levy, and Z. Vogel Cannabinoids {Delta}9-Tetrahydrocannabinol and Cannabidiol Differentially Inhibit the Lipopolysaccharide-activated NF-{kappa}B and Interferon-{beta}/STAT Proinflammatory Pathways in BV-2 Microglial Cells J. Biol. Chem., January 15, 2010; 285(3): 1616 - 1626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nakaya, M. Hashimoto, R. Nakagawa, Y. Wakabayashi, T. Ishizaki, I. Takada, K. Komai, H. Yoshida, and A. Yoshimura SOCS3 in T and NKT Cells Negatively Regulates Cytokine Production and Ameliorates ConA-Induced Hepatitis J. Immunol., December 1, 2009; 183(11): 7047 - 7053. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Lacerda, S. Somers, L. H. Opie, and S. Lecour Ischaemic postconditioning protects against reperfusion injury via the SAFE pathway Cardiovasc Res, November 1, 2009; 84(2): 201 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B Stoffels, J Schmidt, A Nakao, A Nazir, R S Chanthaphavong, and A J Bauer Role of interleukin 10 in murine postoperative ileus Gut, May 1, 2009; 58(5): 648 - 660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Kostianovsky, L. M. Maier, R. C. Anderson, J. N. Bruce, and D. E. Anderson Astrocytic Regulation of Human Monocytic/Microglial Activation J. Immunol., October 15, 2008; 181(8): 5425 - 5432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kitamura, M. Ito, T. Yuasa, C. Kikuguchi, A. Hijikata, M. Takayama, Y. Kimura, R. Yokoyama, T. Kaji, and O. Ohara Genome-wide identification and characterization of transcripts translationally regulated by bacterial lipopolysaccharide in macrophage-like J774.1 cells Physiol Genomics, October 8, 2008; 33(1): 121 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Fielding, R. M. McLoughlin, L. McLeod, C. S. Colmont, M. Najdovska, D. Grail, M. Ernst, S. A. Jones, N. Topley, and B. J. Jenkins IL-6 Regulates Neutrophil Trafficking during Acute Inflammation via STAT3 J. Immunol., August 1, 2008; 181(3): 2189 - 2195. [Abstract] [Full Text] [PDF]
|
|