PMID- 12960255
OWN - NLM
STAT- MEDLINE
DCOM- 20040109
LR  - 20161124
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 74
IP  - 5
DP  - 2003 Nov
TI  - ANP inhibits TNF-alpha-induced endothelial MCP-1 expression--involvement of p38 
      MAPK and MKP-1.
PG  - 932-41
AB  - Atrial natriuretic peptide (ANP) has been shown to reduce tumor necrosis 
      factor-alpha (TNF-alpha)-induced activation of endothelial cells via inhibition 
      of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB 
      pathways. The aim of this study was to determine whether ANP is able to inhibit 
      TNF-alpha-induced expression of monocyte chemoattractant protein-1 (MCP-1) in 
      endothelial cells and to elucidate the mechanisms involved. Pretreatment of human 
      umbilical vein endothelial cells (HUVEC) with ANP significantly reduced 
      TNF-alpha-induced expression of MCP-1 protein and mRNA. The effects of ANP were 
      shown to be mediated via the guanylyl-cyclase (GC)-coupled A receptor. Activation 
      of the other GC-coupled receptor (natriuretic peptide receptor-B) by the C-type 
      natriuretic peptide as well as activation of soluble GC with 
      S-nitroso-L-glutathione (GSNO) exerted similar effects as ANP, supporting a role 
      for cyclic guanosine monophosphate (cGMP) in the signal transduction. Antisense 
      experiments showed a requirement of MAPK phosphatase-1 (MKP-1) induction and 
      therefore, inhibition of p38 MAPK in the ANP-mediated inhibition of 
      TNF-alpha-induced expression of MCP-1. To investigate a potential interplay 
      between TNF-alpha-induced activation of p38 MAPK and NF-kappaB, the p38 MAPK 
      inhibitor SB203580 and a dominant-negative p38 MAPK mutant were used. The results 
      indicated that the blockade of p38 MAPK activity leads to an increased activation 
      of NF-kappaB and therefore, suggest a counter-regulatory action of p38 MAPK and 
      NF-kappaB. As antisense experiments revealed a pivotal role for MKP-1 induction 
      and therefore, p38 MAPK inhibition in ANP-mediated attenuation of MCP-1 
      expression, this action seems to be rather independent of NF-kappaB inhibition.
FAU - Weber, Nina C
AU  - Weber NC
AD  - Department of Pharmacy, University of Munich, Germany.
FAU - Blumenthal, Signe B
AU  - Blumenthal SB
FAU - Hartung, Thomas
AU  - Hartung T
FAU - Vollmar, Angelika M
AU  - Vollmar AM
FAU - Kiemer, Alexandra K
AU  - Kiemer AK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030811
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Nitric Oxide Donors)
RN  - 0 (Pyridines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 57564-91-7 (S-Nitrosoglutathione)
RN  - 85637-73-6 (Atrial Natriuretic Factor)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (Protein Phosphatase 1)
RN  - EC 3.1.3.48 (DUSP1 protein, human)
RN  - EC 3.1.3.48 (Dual Specificity Phosphatase 1)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 4.6.1.2 (Guanylate Cyclase)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Atrial Natriuretic Factor/*pharmacology
MH  - *Cell Cycle Proteins
MH  - Cells, Cultured
MH  - Chemokine CCL2/*genetics
MH  - Dual Specificity Phosphatase 1
MH  - Endothelium, Vascular/drug effects/enzymology/*physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Guanylate Cyclase/metabolism
MH  - Homeostasis
MH  - Imidazoles/pharmacology
MH  - Immediate-Early Proteins/*metabolism
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide Donors/pharmacology
MH  - *Phosphoprotein Phosphatases
MH  - Protein Phosphatase 1
MH  - Protein Tyrosine Phosphatases/*metabolism
MH  - Pyridines/pharmacology
MH  - RNA, Messenger/genetics
MH  - Receptors, Cell Surface/physiology
MH  - S-Nitrosoglutathione/pharmacology
MH  - Signal Transduction/drug effects/physiology
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/*pharmacology
MH  - Umbilical Veins
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2003/09/10 05:00
MHDA- 2004/01/10 05:00
CRDT- 2003/09/10 05:00
PHST- 2003/09/10 05:00 [pubmed]
PHST- 2004/01/10 05:00 [medline]
PHST- 2003/09/10 05:00 [entrez]
AID - jlb.0603254 [pii]
AID - 10.1189/jlb.0603254 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2003 Nov;74(5):932-41. doi: 10.1189/jlb.0603254. Epub 2003 Aug 11.