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

Takafumi Yoshida, Sho ichi Yamagishi, Kazuo Nakamura, Takanori Matsui, Tsutomu Imaizumi, Hiroyoshi Inoue, Takato Ueno, Michio Sata

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

There is a growing body of evidence to show that that C-reactive protein (CRP), an acute phase reactant, is one of the most valuable predictors of future cardiovascular events. Since CRP proteins directly contribute to the development and progression of atherosclerosis as well, reduction of CRP levels may be a novel therapeutic target for the treatment of cardiovascular disease. In this study, we examined whether pigment epithelium-derived factor (PEDF) could block the interleukin-6-induced CRP expression in cultured human hepatoma cells and the way that it might achieve this effect. PEDF inhibited the IL-6-induced CRP expression in Hep3B cells at both mRNA and proteins levels. PEDF suppressed the intracellular reactive oxygen species generation in IL-6-exposed Hep3B cells. Anti-oxidants mimicked the effects of PEDF. PEDF was also found to inhibit the IL-6-elicited Rac-1 activation, whereas dominant-negative Rac-1 dose-dependently decreased the CRP mRNA levels. PEDF blocked the IL-6-induced STAT3 phosphorylations and NF-κB p65 activity in Hep3B cells. Our present study suggests that PEDF could be one of the potent suppressors of CRP production by the liver and may play a protective role against atherosclerosis.

Original languageEnglish
Pages (from-to)1981-1987
Number of pages7
JournalLife Sciences
Volume79
Issue number21
DOIs
Publication statusPublished - 2006 Oct 19
Externally publishedYes

Fingerprint

C-Reactive Protein
Interleukin-6
Chemical activation
Atherosclerosis
Messenger RNA
Phosphorylation
Acute-Phase Proteins
pigment epithelium-derived factor
Oxidants
Liver
Hepatocellular Carcinoma
Reactive Oxygen Species
Proteins
Cardiovascular Diseases
Antioxidants

Keywords

  • Abs
  • antibodies
  • Atherosclerosis
  • C-reactive protein
  • CRP
  • diphenylene iodonium
  • dithiothreitol
  • DPI
  • DTT
  • EC
  • endothelial cells
  • IL-1β
  • IL-6
  • interleukin-1β.
  • interleukin-6
  • Interleukin-6
  • JAK
  • Janus kinase
  • N-acetylcysteine
  • NAC
  • Oxidative stress
  • PEDF
  • pigment epithelium-derived factor
  • reactive oxygen species
  • reverse transcription-polymerase chain reaction
  • ROS
  • RT-PCR
  • signal transducer and activator of transcription
  • STAT

ASJC Scopus subject areas

  • Pharmacology

Cite this

Pigment epithelium-derived factor (PEDF) blocks the interleukin-6 signaling to C-reactive protein expression in Hep3B cells by suppressing Rac-1 activation. / Yoshida, Takafumi; Yamagishi, Sho ichi; Nakamura, Kazuo; Matsui, Takanori; Imaizumi, Tsutomu; Inoue, Hiroyoshi; Ueno, Takato; Sata, Michio.

In: Life Sciences, Vol. 79, No. 21, 19.10.2006, p. 1981-1987.

Research output: Contribution to journalArticle

Yoshida, Takafumi ; Yamagishi, Sho ichi ; Nakamura, Kazuo ; Matsui, Takanori ; Imaizumi, Tsutomu ; Inoue, Hiroyoshi ; Ueno, Takato ; Sata, Michio. / Pigment epithelium-derived factor (PEDF) blocks the interleukin-6 signaling to C-reactive protein expression in Hep3B cells by suppressing Rac-1 activation. In: Life Sciences. 2006 ; Vol. 79, No. 21. pp. 1981-1987.
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AB - There is a growing body of evidence to show that that C-reactive protein (CRP), an acute phase reactant, is one of the most valuable predictors of future cardiovascular events. Since CRP proteins directly contribute to the development and progression of atherosclerosis as well, reduction of CRP levels may be a novel therapeutic target for the treatment of cardiovascular disease. In this study, we examined whether pigment epithelium-derived factor (PEDF) could block the interleukin-6-induced CRP expression in cultured human hepatoma cells and the way that it might achieve this effect. PEDF inhibited the IL-6-induced CRP expression in Hep3B cells at both mRNA and proteins levels. PEDF suppressed the intracellular reactive oxygen species generation in IL-6-exposed Hep3B cells. Anti-oxidants mimicked the effects of PEDF. PEDF was also found to inhibit the IL-6-elicited Rac-1 activation, whereas dominant-negative Rac-1 dose-dependently decreased the CRP mRNA levels. PEDF blocked the IL-6-induced STAT3 phosphorylations and NF-κB p65 activity in Hep3B cells. Our present study suggests that PEDF could be one of the potent suppressors of CRP production by the liver and may play a protective role against atherosclerosis.

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