PMID- 23548612
OWN - NLM
STAT- MEDLINE
DCOM- 20130726
LR  - 20130603
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Linking)
VI  - 304
IP  - 11
DP  - 2013 Jun 1
TI  - Ceramide 1-phosphate induces macrophage chemoattractant protein-1 release: 
      involvement in ceramide 1-phosphate-stimulated cell migration.
PG  - E1213-26
LID - 10.1152/ajpendo.00480.2012 [doi]
AB  - The bioactive sphingolipid ceramide 1-phosphate (C1P) is implicated in 
      inflammatory responses and was recently shown to promote cell migration. However, 
      the mechanisms involved in these actions are poorly described. Using J774A.1 
      macrophages, we have now discovered a new biological activity of C1P: stimulation 
      of monocyte chemoattractant protein-1 (MCP-1) release. This novel effect of C1P 
      was pertussis toxin (PTX) sensitive, suggesting the intervention of Gi 
      protein-coupled receptors. Treatment of the macrophages with C1P caused 
      activation of the phosphatidylinositol 3-kinase (PI3K)/Akt, mitogen-activated 
      protein kinase kinase (MEK)/extracellularly regulated kinases (ERK), and p38 
      pathways. Inhibition of these kinases using selective inhibitors or specific 
      siRNA blocked the stimulation of MCP-1 release by C1P. C1P stimulated nuclear 
      factor-kappaB activity, and blockade of this transcription factor also resulted in 
      complete inhibition of MCP-1 release. Also, C1P stimulated MCP-1 release and cell 
      migration in human THP-1 monocytes and 3T3-L1 preadipocytes. A key observation 
      was that sequestration of MCP-1 with a neutralizing antibody or treatment with 
      MCP-1 siRNA abolished C1P-stimulated cell migration. Also, inhibition of the 
      pathways involved in C1P-stimulated MCP-1 release completely blocked the 
      stimulation of cell migration by C1P. It can be concluded that C1P promotes MCP-1 
      release in different cell types and that this chemokine is a major mediator of 
      C1P-stimulated cell migration. The PI3K/Akt, MEK/ERK, and p38 pathways are 
      important downstream effectors in this action.
FAU - Arana, Lide
AU  - Arana L
AD  - Department of Biochemistry and Molecular Biology, Faculty of Science and 
      Technology, University of the Basque Country (UPV/EHU), Bilbao, Spain.
FAU - Ordonez, Marta
AU  - Ordonez M
FAU - Ouro, Alberto
AU  - Ouro A
FAU - Rivera, Io-Guane
AU  - Rivera IG
FAU - Gangoiti, Patricia
AU  - Gangoiti P
FAU - Trueba, Miguel
AU  - Trueba M
FAU - Gomez-Munoz, Antonio
AU  - Gomez-Munoz A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130402
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Ceramides)
RN  - 0 (Chemokine CCL2)
RN  - 0 (ceramide 1-phosphate)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
SB  - IM
MH  - Cell Line
MH  - Cell Movement/drug effects/*physiology
MH  - Ceramides/*pharmacology
MH  - Chemokine CCL2/*metabolism
MH  - Humans
MH  - MAP Kinase Kinase Kinases/metabolism
MH  - Macrophages/drug effects/*metabolism
MH  - Monocytes/drug effects/*metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Signal Transduction/drug effects/*physiology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
OTO - NOTNLM
OT  - ceramide 1-phosphate
OT  - macrophage migration
OT  - monocyte chemoattractant protein-1 release
OT  - sphingosine 1-phosphate
EDAT- 2013/04/04 06:00
MHDA- 2013/07/28 06:00
CRDT- 2013/04/04 06:00
PHST- 2013/04/04 06:00 [entrez]
PHST- 2013/04/04 06:00 [pubmed]
PHST- 2013/07/28 06:00 [medline]
AID - ajpendo.00480.2012 [pii]
AID - 10.1152/ajpendo.00480.2012 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2013 Jun 1;304(11):E1213-26. doi: 
      10.1152/ajpendo.00480.2012. Epub 2013 Apr 2.