PMID- 12399621
OWN - NLM
STAT- MEDLINE
DCOM- 20030717
LR  - 20171101
IS  - 1660-8151 (Print)
IS  - 1660-8151 (Linking)
VI  - 92
IP  - 4
DP  - 2002 Dec
TI  - Exogenous nitric oxide inhibits tumor necrosis factor-alpha- or 
      interleukin-1-beta-induced monocyte chemoattractant protein-1 expression in human 
      mesangial cells. Role of IkappaB-alpha and cyclic GMP.
PG  - 780-7
AB  - Monocyte chemoattractant protein-1 (MCP-1) plays an important role in 
      glomerulonephritis and nitric oxide (NO) exerts a variety of renal 
      pathophysiological effects. We investigated the effect of exogenous NO on 
      pro-inflammatory cytokine-induced MCP-1 expression in human mesangial cells and 
      its signal transduction pathway. Cells were pretreated with NO donors such as 
      3-morpholino-sydnonimine (SIN-1) or nitroprusside, and then stimulated with tumor 
      necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL-1beta). MCP-1 
      expression of mRNA and protein were measured by Northern blot analysis and ELISA. 
      NF-kappaB binding activity was determined by electrophoretic mobility shift 
      assay. Degradation of IkappaB-alpha protein was assessed by Western blot 
      analysis. SIN-1 inhibited TNF-alpha- or IL-1beta-induced MCP-1 mRNA expression in 
      a dose-dependent manner and also suppressed the MCP-1 protein expression. 
      Nitroprusside inhibited the MCP-1 mRNA expression as well. SIN-1 dose dependently 
      inhibited the TNF-alpha- or IL-1beta-induced NF-kappaB binding activity and 
      suppressed the TNF-alpha-induced degradation of IkappaB-alpha. Analogue of cGMP 
      (8-bromo-cGMP) had no significant effect on TNF-alpha-induced MCP-1 mRNA 
      expression and guanylate cyclase inhibitor (ODQ) also had no significant 
      influence on the inhibitory effect of SIN-1. These results suggest that exogenous 
      NO inhibits MCP-1 expression via suppression of NF-kappaB by reducing the 
      degradation of IkappaB-alpha and through a cGMP-independent pathway.
CI  - Copyright 2002 S. Karger AG, Basel
FAU - Lee, Sang Koo
AU  - Lee SK
AD  - Department of Internal Medicine, Urology, College of Medicine, University of 
      Ulsan, Seoul, Korea. sklee2@amc.seoul.kr
FAU - Kim, Choung Soo
AU  - Kim CS
FAU - Yang, Won Seok
AU  - Yang WS
FAU - Kim, Soon Bae
AU  - Kim SB
FAU - Park, Su-Kil
AU  - Park SK
FAU - Park, Jung Sik
AU  - Park JS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Nephron
JT  - Nephron
JID - 0331777
RN  - 0 (Chemokine CCL2)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Interleukin-1)
RN  - 0 (NF-kappa B)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Nitric Oxide Donors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 169D1260KM (Nitroprusside)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 5O5U71P6VQ (linsidomine)
RN  - D46583G77X (Molsidomine)
RN  - EC 4.6.1.2 (Guanylate Cyclase)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Cyclic GMP/analogs & derivatives/antagonists & inhibitors/metabolism
MH  - Glomerular Mesangium/cytology/*drug effects/metabolism
MH  - Guanylate Cyclase/metabolism
MH  - Humans
MH  - I-kappa B Proteins/*metabolism
MH  - Interleukin-1/*pharmacology
MH  - Molsidomine/*analogs & derivatives/pharmacology
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/antagonists & inhibitors/metabolism
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Donors/pharmacology
MH  - Nitroprusside/pharmacology
MH  - Protein Binding
MH  - RNA, Messenger/metabolism
MH  - Signal Transduction/physiology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2002/10/26 04:00
MHDA- 2003/07/18 05:00
CRDT- 2002/10/26 04:00
PHST- 2002/10/26 04:00 [pubmed]
PHST- 2003/07/18 05:00 [medline]
PHST- 2002/10/26 04:00 [entrez]
AID - 65441 [pii]
AID - 10.1159/000065441 [doi]
PST - ppublish
SO  - Nephron. 2002 Dec;92(4):780-7. doi: 10.1159/000065441.