Pigment epithelium-derived factor (PEDF) blocks the interleukin-6 signaling to C-reactive protein expression in Hep3B cells by suppressing Rac-1 activation

Life Sciences ◽  
2006 ◽  
Vol 79 (21) ◽  
pp. 1981-1987 ◽  
Author(s):  
Takafumi Yoshida ◽  
Sho-ichi Yamagishi ◽  
Kazuo Nakamura ◽  
Takanori Matsui ◽  
Tsutomu Imaizumi ◽  
...  
1995 ◽  
Vol 310 (1) ◽  
pp. 143-148 ◽  
Author(s):  
D Zhang ◽  
S L Jiang ◽  
D Rzewnicki ◽  
D Samols ◽  
I Kushner

The combination of interleukin 6 (IL-6) and interleukin 1 (IL-1) synergistically induces the human acute-phase reactant, C-reactive protein (CRP) in Hep3B cells. While previous studies have indicated that IL-6 induces transcription of CRP, the mode of action of IL-1 has not been clearly defined. It has been suggested that the effect of IL-1 might be post-transcriptional, exerted through the 5′-untranslated region (5′-UTR). To evaluate the role of IL-1 in CRP gene expression, we studied the effects of interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) on both the endogenous CRP gene and on transfected CRP-CAT constructs in Hep3B cells. In kinetic studies of the endogenous CRP gene, IL-1 beta alone had no effect on CRP mRNA levels, but when added to IL-6, synergistically enhanced both CRP mRNA levels and transcription, as determined by Northern-blot analyses and nuclear run-on studies. IL-6 alone and the combination of [IL-1 beta + IL-6] each induced increases in mRNA levels roughly comparable with observed increases in transcription. These findings indicate that the effect of IL-1 beta on CRP expression is exerted largely at the transcriptional level in this system. This conclusion was confirmed by studies in Hep3B cells transiently transfected with CRP-CAT constructs, each containing 157 bp of the CRP 5′-flanking region but differing in the length of the 5′-UTR from 104 bp to 3 bp. All constructs responded in the same way; IL-6, but not IL-1 beta, induced significant chloramphenicol acetyltransferase (CAT) expression which was synergistically enhanced 2- to 3-fold by IL-1 beta. These results indicate that IL-1 beta stimulates transcriptional events in the presence of IL-6 and that the upstream 157 bases of the CRP promoter contain elements capable of both IL-6 induction and the synergistic effect of IL-1 beta on transcription.


2009 ◽  
Vol 379 (2) ◽  
pp. 476-479 ◽  
Author(s):  
Songwen Zhang ◽  
Qiangyuan Liu ◽  
Juan Wang ◽  
Douglas C. Harnish

2015 ◽  
Vol 41 (4) ◽  
pp. 464-469 ◽  
Author(s):  
Mauricio Garrido ◽  
Andrea Dezerega ◽  
María José Bordagaray ◽  
Montserrat Reyes ◽  
Rolando Vernal ◽  
...  

2006 ◽  
Vol 7 (3) ◽  
pp. 570
Author(s):  
C.M. Mayer ◽  
H.-J. Gruber ◽  
E.-M. Landl ◽  
S. Pailer ◽  
H. Scharnagl ◽  
...  

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