PMID- 16288471
OWN - NLM
STAT- MEDLINE
DCOM- 20060605
LR  - 20191210
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 207
IP  - 1
DP  - 2006 Apr
TI  - Transcriptional regulation of VCAM-1 expression by tumor necrosis factor-alpha in 
      human tracheal smooth muscle cells: involvement of MAPKs, NF-kappaB, p300, and 
      histone acetylation.
PG  - 174-86
AB  - Tumor necrosis factor-alpha (TNF-alpha) has been shown to induce the expression 
      of adhesion molecules in airway resident cells and contribute to inflammatory 
      responses. Here, the roles of mitogen-activated protein kinases (MAPKs) and 
      NF-kappaB in TNF-alpha-induced expression of vascular cell adhesion molecule 
      (VCAM)-1 were investigated in human tracheal smooth muscle cells (HTSMCs). 
      TNF-alpha-enhanced expression of VCAM-1 protein and mRNA as well as 
      phosphorylation of p42/p44 MAPK, p38, and JNK were significantly attenuated by 
      inhibitors of MEK1/2 (U0126), p38 (SB202190), and JNK (SP600125). Transfection 
      with dominant negative mutants of MEK1/2, ERK1, ERK2, p38, and JNK attenuated 
      TNF-alpha-induced VCAM-1 expression. Furthermore, TNF-alpha-induced VCAM-1 
      expression was significantly blocked by a selective NF-kappaB inhibitor 
      helenalin. TNF-alpha-stimulated translocation of NF-kappaB into the nucleus and 
      degradation of IkappaB-alpha was blocked by helenalin, but not by U0126, 
      SB202190, or SP600125. VCAM-1 promoter activity was enhanced by TNF-alpha in 
      HTSMCs transfected with VCAM-1-Luc, which was inhibited by helenalin, U0126, 
      SB202190, and SP600125. Most surprisingly, VCAM-1 expression was also 
      significantly blocked by a selective inhibitor of p300, curcumin. NF-kappaB 
      transcription factor and p300 were associated with the VCAM-1 promoter, which was 
      dynamically linked to histone H3 acetylation stimulated by TNF-alpha, as 
      determined by chromatin immunoprecipitation assay. Moreover, the resultant 
      enhancement of VCAM-1 expression increased the adhesion of polymorphonuclear 
      cells (PMNs) to monolayer of HTSMCs, which was blocked by helenalin, U0126, 
      SB202190, or SP600125. These results suggest that in HTSMCs, activation of MAPK 
      pathways, NF-kappaB, and p300 is essential for TNF-alpha-induced VCAM-1 
      expression.
FAU - Lee, Chiang-Wen
AU  - Lee CW
AD  - Department of Pharmacology, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan.
FAU - Lin, Wei-Ning
AU  - Lin WN
FAU - Lin, Chih-Chung
AU  - Lin CC
FAU - Luo, Shue-Fen
AU  - Luo SF
FAU - Wang, Jong-Shyan
AU  - Wang JS
FAU - Pouyssegur, Jacques
AU  - Pouyssegur J
FAU - Yang, Chuen-Mao
AU  - Yang CM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Butadienes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Histones)
RN  - 0 (NF-kappa B)
RN  - 0 (Nitriles)
RN  - 0 (Sesquiterpenes)
RN  - 0 (Sesquiterpenes, Guaiane)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (U 0126)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 4GUY9L896T (helenalin)
RN  - 9007-49-2 (DNA)
RN  - EC 2.3.1.48 (p300-CBP Transcription Factors)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Acetylation
MH  - Butadienes/pharmacology
MH  - Cell Adhesion/drug effects
MH  - Cells, Cultured
MH  - Chromatin Immunoprecipitation
MH  - Curcumin/pharmacology
MH  - DNA/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation/*drug effects
MH  - Histones/metabolism
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & 
      inhibitors/genetics/metabolism
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/genetics/metabolism
MH  - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/genetics/metabolism
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/genetics/metabolism
MH  - Models, Biological
MH  - Mutation/genetics
MH  - Myocytes, Smooth Muscle/cytology/*drug effects/metabolism
MH  - NF-kappa B/antagonists & inhibitors/metabolism
MH  - Neutrophils/cytology/drug effects/metabolism
MH  - Nitriles/pharmacology
MH  - Phosphorylation/drug effects
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding
MH  - Sesquiterpenes/pharmacology
MH  - Sesquiterpenes, Guaiane
MH  - Signal Transduction/drug effects
MH  - Time Factors
MH  - Trachea/cytology
MH  - Transcription, Genetic/drug effects
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Vascular Cell Adhesion Molecule-1/*genetics/metabolism
MH  - p300-CBP Transcription Factors/antagonists & inhibitors/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & 
      inhibitors/genetics/metabolism
EDAT- 2005/11/17 09:00
MHDA- 2006/06/06 09:00
CRDT- 2005/11/17 09:00
PHST- 2005/11/17 09:00 [pubmed]
PHST- 2006/06/06 09:00 [medline]
PHST- 2005/11/17 09:00 [entrez]
AID - 10.1002/jcp.20549 [doi]
PST - ppublish
SO  - J Cell Physiol. 2006 Apr;207(1):174-86. doi: 10.1002/jcp.20549.