PMID- 10433212
OWN - NLM
STAT- MEDLINE
DCOM- 19990817
LR  - 20161124
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 140
IP  - 8
DP  - 1999 Aug
TI  - Intracellular signaling in rat cultured vascular smooth muscle cells: roles of 
      nuclear factor-kappaB and p38 mitogen-activated protein kinase on tumor necrosis 
      factor-alpha production.
PG  - 3562-72
AB  - Lipopolysaccharide (LPS) is responsible for initiating host responses leading to 
      septic shock, and tumor necrosis factor-alpha (TNF alpha) is thought to be its 
      primary mediator. In addition, TNF alpha is one of the major components of the 
      pathogenesis of insulin resistance in various conditions. It has been shown that 
      LPS induced TNF alpha production in rat vascular smooth muscle cells (VSMC). 
      However, little is known about the signaling pathway by which VSMC in culture 
      produce TNF alpha. We investigated the possible signaling components involved in 
      this pathway. LPS elicited phosphorylation of p42/44 mitogen-activated protein 
      kinase (MAPK) and p38 MAPK, degradation of inhibitor of kappaB (IkappaB), and an 
      increase in nuclear binding activity of activating protein-1 and nuclear 
      factor-kappaB (NF-kappaB). Different types of NF-kappaB inhibitors, pyrrolidine 
      dithiocarbamate and MG132, which specifically abolished IkappaB degradation and 
      subsequent NF-kappaB activation by LPS, suppressed TNF alpha secretion from VSMC. 
      Although PD98059, a specific MAPK kinase inhibitor and SB203580, a specific p38 
      MAPK inhibitor, had no effect on NF-kappaB activity, SB203580 suppressed TNF 
      alpha secretion; however, PD98059 did not. A cotransfection assay showed that 
      transfection of dominant negative IkappaB or pretreatment with SB203580 
      suppressed the TNF alpha gene promotor-dependent transcription. TNF alpha 
      messenger RNA expression induced by LPS was inhibited by pyrrolidine 
      dithiocarbamate, MG132, and SB203580, but not by PD98059. These observations 
      indicate that TNF alpha production in VSMC is stimulated by LPS, and its 
      transcription and translation are dependent on NF-kappaB activation through 
      proteasome-mediated IkappaB degradation. It is likely that p38 MAPK may play a 
      critical role in regulating transcription of the TNF alpha gene in VSMC, unlike 
      in other cell lines.
FAU - Yamakawa, T
AU  - Yamakawa T
AD  - Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, 
      Tennessee 37232, USA.
FAU - Eguchi, S
AU  - Eguchi S
FAU - Matsumoto, T
AU  - Matsumoto T
FAU - Yamakawa, Y
AU  - Yamakawa Y
FAU - Numaguchi, K
AU  - Numaguchi K
FAU - Miyata, I
AU  - Miyata I
FAU - Reynolds, C M
AU  - Reynolds CM
FAU - Motley, E D
AU  - Motley ED
FAU - Inagami, T
AU  - Inagami T
LA  - eng
GR  - HL-03320/HL/NHLBI NIH HHS/United States
GR  - HL-35323/HL/NHLBI NIH HHS/United States
GR  - HL-58205/HL/NHLBI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Pyridines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent 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  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Animals
MH  - Aorta, Thoracic/cytology/physiology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cell Communication/physiology
MH  - Cells, Cultured
MH  - Enzyme Inhibitors/pharmacology
MH  - *Gene Expression Regulation/drug effects
MH  - Imidazoles/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3
MH  - *Mitogen-Activated Protein Kinases
MH  - Muscle, Smooth, Vascular/cytology/drug effects/*physiology
MH  - NF-kappa B/*metabolism
MH  - Pyridines/pharmacology
MH  - RNA, Messenger/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/*physiology
MH  - Transcription, Genetic
MH  - Tumor Necrosis Factor-alpha/analysis/*genetics/pharmacology
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 1999/08/05 00:00
MHDA- 1999/08/05 00:01
CRDT- 1999/08/05 00:00
PHST- 1999/08/05 00:00 [pubmed]
PHST- 1999/08/05 00:01 [medline]
PHST- 1999/08/05 00:00 [entrez]
AID - 10.1210/endo.140.8.6914 [doi]
PST - ppublish
SO  - Endocrinology. 1999 Aug;140(8):3562-72. doi: 10.1210/endo.140.8.6914.