PMID- 15864742
OWN - NLM
STAT- MEDLINE
DCOM- 20051027
LR  - 20081121
IS  - 1021-7770 (Print)
IS  - 1021-7770 (Linking)
VI  - 12
IP  - 1
DP  - 2005
TI  - ICAM-1 induction by TNFalpha and IL-6 is mediated by distinct pathways via Rac in 
      endothelial cells.
PG  - 91-101
AB  - Atherogenesis is a chronic inflammatory response and intercellular adhesion 
      molecule (ICAM-1) induced by cytokines plays a role in this event. In this study, 
      the molecular mechanisms of tumor neurosis factor alpha (TNFalpha)- and 
      IL-6-induced ICAM-1 gene expression in endothelial cells (ECs) were examined. ECs 
      infected with adenovirus carrying the dominant negative mutant of Rac (Ad-RacN17) 
      exhibited inhibition in both TNFalpha- and IL-6-induced ICAM-1 expression. 
      Consistently, ECs transfected with RacN17 inhibited both TNFalpha- and 
      IL-6-induced ICAM-1 promoter activities. Functional analysis of ICAM-1 promoter, 
      however, indicated that the cis-acting elements in response to TNFalpha and IL-6 
      are different. The NFkappaB binding site in the ICAM-1 promoter region was 
      crucial for TNFalpha-induced ICAM-1 expression but not for the induction by IL-6. 
      ECs infected with Ad-RacN17 attenuated the TNFalpha-induced NFkappaB binding 
      activity. In contrast, IL-6 activated a transcriptional factor, signal transducer 
      and activator of transcription-3 (Stat3) via the phosphorylation of Tyr705 at 
      Stat3. ECs transfected with the dominant negative mutant of Stat3 (Stat3F) 
      demonstrated that Stat3 was required for IL-6-induced ICAM-1 gene expression. 
      Interestingly, the phosphorylation of Tyr705 and Ser727 in Stat3 was greatly 
      inhibited in IL-6-treated ECs previously infected with Ad-RacN17. Our data 
      strongly indicated that ICAM-1 gene induction by TNFalpha and IL-6 is mediated 
      mainly via NFkappaB and Stat3, respectively and Rac1 appears to play a central 
      role in modulating cytokine-induced ICAM-1 expression in ECs.
FAU - Wung, B S
AU  - Wung BS
AD  - Department of Applied Microbiology, National Chiayi University, Chiayi, Taiwan.
FAU - Ni, C W
AU  - Ni CW
FAU - Wang, D L
AU  - Wang DL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Biomed Sci
JT  - Journal of biomedical science
JID - 9421567
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/metabolism
MH  - Endothelial Cells/cytology/*drug effects/metabolism
MH  - Endothelium, Vascular/cytology
MH  - *Gene Expression Regulation
MH  - Genes, Reporter
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/*genetics/metabolism
MH  - Interleukin-6/*pharmacology
MH  - NF-kappa B/metabolism
MH  - Promoter Regions, Genetic
MH  - Protein Binding
MH  - RNA, Messenger/metabolism
MH  - STAT3 Transcription Factor
MH  - Signal Transduction/*physiology
MH  - Trans-Activators/metabolism
MH  - Transcriptional Activation
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - rac1 GTP-Binding Protein/genetics/*metabolism
EDAT- 2005/05/03 09:00
MHDA- 2005/10/28 09:00
CRDT- 2005/05/03 09:00
PHST- 2004/05/13 00:00 [received]
PHST- 2004/10/08 00:00 [accepted]
PHST- 2005/05/03 09:00 [pubmed]
PHST- 2005/10/28 09:00 [medline]
PHST- 2005/05/03 09:00 [entrez]
AID - 10.1007/s11373-004-8170-z [doi]
PST - ppublish
SO  - J Biomed Sci. 2005;12(1):91-101. doi: 10.1007/s11373-004-8170-z.