PMID- 16636588
OWN - NLM
STAT- MEDLINE
DCOM- 20060802
LR  - 20170118
IS  - 1660-2129 (Electronic)
IS  - 1660-2129 (Linking)
VI  - 103
IP  - 4
DP  - 2006
TI  - Proinflammatory cytokine-induced NF-kappaB activation in human mesangial cells is 
      mediated through intracellular calcium but not ROS: effects of silymarin.
PG  - e156-65
AB  - BACKGROUND: It is not fully understood whether intracellular calcium and/or 
      reactive oxygen species (ROS) are involved in nuclear factor-kappaB (NF-kappaB) 
      activation by proinflammatory cytokines. Silymarin exhibits anti-inflammatory and 
      antioxidant effects but the effect of silymarin in human mesangial cells is 
      largely unknown. METHOD: NF-kappaB binding activity was measured by 
      electrophoretic mobility shift assay. Intracellular calcium was monitored by 
      confocal microscopy using Fluo-3 and intracellular ROS production was determined 
      by flow cytometry. Monocyte chemoattractant protein-1 (MCP-1) expression was 
      measured by Northern blot analysis and ELISA. RESULTS: NF-kappaB was activated 
      within 30 min by tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta 
      (IL-1beta). Intracellular ROS was not produced until 30 min and also antioxidants 
      such as N-acetylcysteine and tiron had no effect on the TNF-alpha- or 
      IL-1beta-induced NF-kappaB activation. Intracellular calcium was increased by 
      TNF-alpha and IL-1beta. Furthermore, a calcium chelator, BAPTA-AM, attenuated the 
      NF-kappaB activation. Silymarin dose-dependently inhibited the TNF-alpha- or 
      IL-1beta-induced NF-kappaB activation and MCP-1 expression. Silymarin also 
      inhibited TNF-alpha-induced intracellular calcium. CONCLUSIONS: Induction of 
      NF-kappaB within 30 min by TNF-alpha- and IL-1beta was mediated through 
      intracellular calcium but not ROS. Silymarin inhibited TNF-alpha-induced 
      calcium-dependent NF-kappaB activation irrespective of its antioxidant effect.
CI  - Copyright 2006 S. Karger AG, Basel
FAU - Chang, Jai Wong
AU  - Chang JW
AD  - Department of Internal Medicine, Urology and Asan Institute for Life Sciences, 
      College of Medicine, University of Ulsan, Seoul, Korea.
FAU - Kim, Choung Soo
AU  - Kim CS
FAU - Kim, Soon Bae
AU  - Kim SB
FAU - Park, Su Kil
AU  - Park SK
FAU - Park, Jung Sik
AU  - Park JS
FAU - Lee, Sang Koo
AU  - Lee SK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060421
PL  - Switzerland
TA  - Nephron Exp Nephrol
JT  - Nephron. Experimental nephrology
JID - 101159770
RN  - 0 (Antioxidants)
RN  - 0 (Interleukin-1)
RN  - 0 (NF-kappa B)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Silymarin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Antioxidants/*pharmacology
MH  - Blotting, Northern
MH  - Calcium/*physiology
MH  - Cell Culture Techniques
MH  - Electrophoretic Mobility Shift Assay
MH  - Humans
MH  - Immunohistochemistry
MH  - Inflammation
MH  - Interleukin-1/physiology
MH  - Mesangial Cells/*drug effects/*physiology
MH  - NF-kappa B/*metabolism
MH  - Reactive Oxygen Species
MH  - Signal Transduction/drug effects
MH  - Silymarin/*pharmacology
MH  - Tumor Necrosis Factor-alpha/physiology
EDAT- 2006/04/26 09:00
MHDA- 2006/08/03 09:00
CRDT- 2006/04/26 09:00
PHST- 2005/03/10 00:00 [received]
PHST- 2006/01/13 00:00 [accepted]
PHST- 2006/04/26 09:00 [pubmed]
PHST- 2006/08/03 09:00 [medline]
PHST- 2006/04/26 09:00 [entrez]
AID - 92906 [pii]
AID - 10.1159/000092906 [doi]
PST - ppublish
SO  - Nephron Exp Nephrol. 2006;103(4):e156-65. doi: 10.1159/000092906. Epub 2006 Apr 
      21.