PMID- 15271789
OWN - NLM
STAT- MEDLINE
DCOM- 20050324
LR  - 20171116
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 24
IP  - 10
DP  - 2004 Oct
TI  - Leukotriene B4 strongly increases monocyte chemoattractant protein-1 in human 
      monocytes.
PG  - 1783-8
AB  - OBJECTIVE: Leukotriene B4 (LTB4), a product of the 5-lipoxygenase (5-LO) pathway 
      of arachidonic acid metabolism, has been implicated in atherosclerosis. However, 
      the molecular mechanisms for the atherogenic effect of LTB4 are not well 
      understood. This study is to determine candidate mechanisms. METHOD AND RESULTS: 
      Primary human monocytes were treated with LTB4 and the supernatant was analyzed 
      for cytokine/chemokine production by an immuno-protein array. This analysis 
      revealed a strong increase of the monocyte chemoattractant protein-1 (MCP-1), a 
      proinflammatory cytokine. Follow-up analyses with MCP-1 enzyme-linked 
      immunosorbent assay (for quantitation of MCP-1 protein) and real-time polymerase 
      chain reaction (PCR) (for MCP-1 mRNA) demonstrated that LTB4 strongly induced 
      expression of MCP-1 protein and mRNA in a time-dependent and dose-dependent 
      fashion. This induction was effectively abolished by CP-105,696, an antagonist 
      for the LTB4 receptor BLT1. Selective inhibitors of ERK1/2 or JNK MAPK 
      effectively blocked the LTB4-induced MCP-1 production. Furthermore, LTB4 
      increased NF-[kappa]B DNA binding activity, which was blocked by CP-105,696. 
      CONCLUSIONS: LTB4 strongly induces MCP-1 production in primary human monocytes. 
      This induction is mediated through the BLT1 pathway increasing MCP-1 
      transcription. Activation of ERK1/2 or JNK MAPK is essential for this induction. 
      The NF-[kappa]B activation may be involved in LTB4-increased MCP-1 expression. 
      The LTB4-induced MCP-1 in human monocytes may play a critical role in the 
      atherogenicity of LTB4.
FAU - Huang, Li
AU  - Huang L
AD  - Department of Cardiovascular Diseases, Merck Research Laboratories, Rahway, NJ 
      07065, USA.
FAU - Zhao, Annie
AU  - Zhao A
FAU - Wong, Frederick
AU  - Wong F
FAU - Ayala, Julia M
AU  - Ayala JM
FAU - Struthers, Mary
AU  - Struthers M
FAU - Ujjainwalla, Feroze
AU  - Ujjainwalla F
FAU - Wright, Samuel D
AU  - Wright SD
FAU - Springer, Marty S
AU  - Springer MS
FAU - Evans, Jilly
AU  - Evans J
FAU - Cui, Jisong
AU  - Cui J
LA  - eng
PT  - Journal Article
DEP - 20040722
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Benzopyrans)
RN  - 0 (Carboxylic Acids)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Leukotriene B4)
RN  - 1HGW4DR56D (Leukotriene B4)
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  - Z7354TW4BM (CP 105696)
SB  - IM
CIN - Arterioscler Thromb Vasc Biol. 2004 Oct;24(10):1748-9. PMID: 15472137
MH  - Benzopyrans/pharmacology
MH  - Carboxylic Acids/pharmacology
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors
MH  - Leukotriene B4/*pharmacology
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors
MH  - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors
MH  - Monocytes/*drug effects/enzymology
MH  - NF-kappa B/metabolism
MH  - Receptors, Leukotriene B4/antagonists & inhibitors
MH  - Transcription, Genetic/drug effects
EDAT- 2004/07/24 05:00
MHDA- 2005/03/25 09:00
CRDT- 2004/07/24 05:00
PHST- 2004/07/24 05:00 [pubmed]
PHST- 2005/03/25 09:00 [medline]
PHST- 2004/07/24 05:00 [entrez]
AID - 01.ATV.0000140063.06341.09 [pii]
AID - 10.1161/01.ATV.0000140063.06341.09 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2004 Oct;24(10):1783-8. doi: 
      10.1161/01.ATV.0000140063.06341.09. Epub 2004 Jul 22.