| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
B on the Proximal Promoter
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614
C-reactive protein (CRP) is an acute phase protein produced by hepatocytes. A minor elevation in the baseline levels of serum CRP is considered an indicator of chronic inflammation. In hepatoma Hep3B cells, IL-6 induces CRP expression by activating transcription factors STAT3 and C/EBP
. IL-1 synergistically enhances the effects of IL-6. The first 157 bp of the CRP promoter are sufficient for IL-1 synergy. Previously, NF-
B, a transcription factor activated by IL-1 in Hep3B cells, has been shown to increase endogenous CRP expression. The purpose of this study was to investigate the possible action of NF-B on the 157 bp of the proximal promoter. In this study we show that NF-B requires and acts synergistically with C/EBP on the CRP-proximal promoter to regulate CRP expression. We located the regulatory element that consisted of overlapping binding sites for NF-B (p50-p50 and p50-p65) and OCT-1. The B site was responsible for the synergy between NF-B and C/EBP and was also necessary for the CRP transactivation by C/EBP through the C/EBP site. Mutation of the B site decreased the synergistic effect of IL-1 on IL-6-induced CRP expression. Basal CRP expression increased dramatically when binding of both OCT-1 and NF-B was abolished. Combined data from luciferase transactivation assays and EMSA lead us to conclude that the binding of OCT-1 to the promoter, facilitated by p50-p50 in a novel way, represses, whereas replacement of OCT-1 by p50-p65 induces CRP transcription in cooperation with C/EBP. This model for CRP expression favors the variation seen in baseline serum CRP levels in a normal healthy population.
This article has been cited by other articles:
|
|
 |
|
  J. Kang, M. Gemberling, M. Nakamura, F. G. Whitby, H. Handa, W. G. Fairbrother, and D. Tantin A general mechanism for transcription regulation by Oct1 and Oct4 in response to genotoxic and oxidative stress Genes & Dev., January 15, 2009; 23(2): 208 - 222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nishikawa, K. Hagihara, S. Serada, T. Isobe, A. Matsumura, J. Song, T. Tanaka, I. Kawase, T. Naka, and K. Yoshizaki Transcriptional Complex Formation of c-Fos, STAT3, and Hepatocyte NF-1{alpha} Is Essential for Cytokine-Driven C-Reactive Protein Gene Expression J. Immunol., March 1, 2008; 180(5): 3492 - 3501. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Puel, C. Picard, M. Lorrot, C. Pons, M. Chrabieh, L. Lorenzo, M. Mamani-Matsuda, E. Jouanguy, D. Gendrel, and J.-L. Casanova Recurrent Staphylococcal Cellulitis and Subcutaneous Abscesses in a Child with Autoantibodies against IL-6 J. Immunol., January 1, 2008; 180(1): 647 - 654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. N. Patel, C. A. King, S. R. Bailey, J. W. Holt, K. Venkatachalam, A. Agrawal, A. J. Valente, and B. Chandrasekar Interleukin-17 Stimulates C-reactive Protein Expression in Hepatocytes and Smooth Muscle Cells via p38 MAPK and ERK1/2-dependent NF-{kappa}B and C/EBPbeta Activation J. Biol. Chem., September 14, 2007; 282(37): 27229 - 27238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. P. Singh, B. Voleti, and A. Agrawal A Novel RBP-J{kappa}-Dependent Switch from C/EBPbeta to C/EBP{zeta} at the C/EBP Binding Site on the C-Reactive Protein Promoter J. Immunol., June 1, 2007; 178(11): 7302 - 7309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Blaschke, Y. Takata, E. Caglayan, A. Collins, P. Tontonoz, W. A. Hsueh, and R. K. Tangirala A Nuclear Receptor Corepressor-Dependent Pathway Mediates Suppression of Cytokine-Induced C-Reactive Protein Gene Expression by Liver X Receptor Circ. Res., December 8, 2006; 99(12): e88 - e99. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
