scholarly journals The effect of interleukin-1 on C-reactive protein expression in Hep3B cells is exerted at the transcriptional level

1995 ◽  
Vol 310 (1) ◽  
pp. 143-148 ◽  
Author(s):  
D Zhang ◽  
S L Jiang ◽  
D Rzewnicki ◽  
D Samols ◽  
I Kushner
Keyword(s):  
Interleukin 6 ◽  
Interleukin 1 ◽  
Kinetic Studies ◽  
Acute Phase Reactant ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Hep3b Cells

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.

C-Reactive Protein, Interleukin 6, and N-Terminal Pro-Brain Natriuretic Peptide Following Cardioversion of Atrial Fibrillation: Is There a Role of Biomarkers in Arrhythmia Recurrence?

Angiology ◽  
2010 ◽  
Vol 62 (4) ◽  
pp. 310-316 ◽  
Author(s):  
Stavroula N. Psychari ◽  
Dionyssios Chatzopoulos ◽  
Efstathios K. Iliodromitis ◽  
Thomas S. Apostolou ◽  
Dimitrios T. Kremastinos
Keyword(s):  
Atrial Fibrillation ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Interleukin 6 ◽  
C Reactive Protein ◽  
Reactive Protein

Abstract 277: Elevated C-Reactive Protein Contributes to Preeclampsia via Kinin Signaling Pathways

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Nicholas Parchim ◽  
Wei Wang ◽  
Takayuki Iriyama ◽  
Chen Liu ◽  
Athar H Siddiqui ◽  
...  
Keyword(s):  
Acute Phase Reactant ◽  
Receptor Activation ◽  
C Reactive Protein ◽  
Direct Role ◽  
Human Trophoblast ◽  
Reactive Protein ◽  
Induced Hypertension ◽  
Pregnant Mice

Preeclampsia (PE) is a serious pregnancy disease characterized by hypertension and proteinuria. Despite intensive research efforts, the underlying cause of PE remains a mystery. PE is, however, associated with abnormalities of the immune system. Here we report that the levels of C-reactive protein (CRP), an important acute phase reactant, were significantly elevated in the plasma of human with PE at the third trimester. Next, we found that CRP protein levels in the placentas of PE patients were also significantly increased compared to controls. In an effort to determine the exact role of elevated CRP in PE, we infused CRP into pregnant mice. We found that injection of CRP into pregnant mice induced hypertension (170 mmHg mean systolic vs. 125 mmHg mean systolic control; p<0.05) and proteinuria (25 mg/ug vs 12 mg/ug vehicle; p<0.05), indicating the direct role of CRP in PE. CRP is known to bind with phosphocholine on damaged cell membranes. Recent studies identified that neurokinin B (NKB), a placental enriched neuropeptide and known pathogenic molecule for PE, is phosphocholinated. This posttranslational modification increases its stability and enhances NKB-mediated receptor activation. These findings raise an intriguing hypothesis that CRP may bind with NKB coupled to NK3R activation and contribute to PE. To test this hypothesis, we conducted a pulldown assay, and we found that CRP bound with NKB. Next, using a cellular invasion assay, we revealed that CRP decreased invasion of human trophoblast cells (0.7 to 0.07 invasion index, p<0.05), while treatment with an NK3R selective antagonist, SB222200, ameliorated this shallow invasion. Finally, we provided in vivo evidence that inhibition of NK3R by SB222200 or knockdown of NK3R by specific siRNA in a potent nanoparticle delivery system significantly reduced CRP-induced hypertension and proteinuria in pregnant mice (170 mmHg mean systolic CRP-injected vs. 130 mmHg mean systolic siRNA NK3R; p<0.05 and proteinuria 25 mg/ug vs. 15 mg/ug; p<0.05). Overall, our findings demonstrate that elevated CRP contributes to PE and NKB/NK3R is a novel mechanism underlying CRP-mediated shallow invasion and disease development. These studies suggest novel pathogenic biomarkers and innovative therapeutic targets for PE.

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 ◽  
...  
Keyword(s):  
Protein Expression ◽  
Interleukin 6 ◽  
Pigment Epithelium ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Pigment Epithelium Derived Factor ◽  
Hep3b Cells

scholarly journals The Role of C-reactive Protein and Interleukin 6 in the Cases of Preeclampsia Associated with Obesity

2019 ◽  
Vol 70 (3) ◽  
pp. 805-808 ◽  
Author(s):  
Izabella Petre ◽  
Marius Craina ◽  
Nicolae Suciu ◽  
Alina Sisu ◽  
Radu Dumitru Moleriu ◽  
...  
Keyword(s):  
Risk Factor ◽  
Early Detection ◽  
Pregnant Women ◽  
Interleukin 6 ◽  
Inflammatory Markers ◽  
Inflammatory Condition ◽  
European Level ◽  
C Reactive Protein ◽  
Reactive Protein

In the management of preeclampsia/eclampsia, it would be useful at least at European level, to have clear protocols for early detection and approach of cases with hypertension, as well as to create an algorithm to identify the predisposition to hypertensive pregnancy pathology. The aim has been to identify the favorable factors and the evolution of the pregnancy in the 100 patients admitted to the obstetrics clinic between January 2014 and December 2018, aged between 15-44 years, who have been diagnosed with preeclampsia. In recent years, the management of pregnant women with preeclampsia has improved a lot due to a better understanding of the pathogenesis and a refinement of adequate pregnancy monitoring. Obesity has been shown to be a risk factor in preeclampsia. Several studies have identified preeclampsia as an inflammatory condition. A large number of inflammatory markers, such as C-reactive protein (PCR) and Interleukin 6 (IL-6), have been shown to be elevated in pregnant women with preeclampsia.

scholarly journals Cloning and tissue-specific expression of the gene for mouse C-reactive protein

1993 ◽  
Vol 295 (2) ◽  
pp. 379-386 ◽  
Author(s):  
N O Ku ◽  
R F Mortensen
Keyword(s):  
Acute Phase ◽  
Transcriptional Start Site ◽  
Interleukin 1 ◽  
Acute Phase Reactant ◽  
C Reactive Protein ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression ◽  
Reactive Protein ◽  
Phase Reactant

C-reactive protein is a serum acute-phase reactant that increases several thousand-fold in concentration during inflammation in most mammals. However, mouse C-reactive protein is considered to be a minor acute-phase reactant, since its blood level increases only from approx. 0.1 to 1-2 micrograms/ml. A mouse genomic clone of approximately 5 kb was obtained to determine the molecular basis for the regulation of the expression of mouse C-reactive protein. Several cis-acting elements in the 5′ flanking region that potentially regulate transcription were identified: two glucocorticoid-responsive elements, two CCAAT-enhancer-binding protein C (C/EBP) consensus elements that are required for the interleukin-1 responsiveness of some acute-phase reactant genes, an interleukin-6-responsive element, two hepatocyte nuclear factor-1 (HNF-1) elements and a single heat-shock element. Transfection of the hepatoma cell line Hep 3B.2 with a pCAT expression vector containing the 5′ flanking sequence from -1083 to -3 bp from the transcriptional start site, and truncations of this sequence, localized elements that control the tissue-specific expression of mouse C-reactive protein to the two HNF-1 elements and a C/EBP, interleukin-1-responsive element located between -220 and -153, and -90 and -50 bp from the transcriptional start site. A constitutive nuclear protein from mouse-liver hepatocytes specifically binds to the HNF-1 elements. These findings explain the tissue-specific expression of the gene, as well as its limited expression during the acute-phase response.

Sign in / Sign up

Export Citation Format

Share Document