PMID- 23185512
OWN - NLM
STAT- MEDLINE
DCOM- 20130530
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 11
DP  - 2012
TI  - The CCL2/CCR2 axis enhances vascular cell adhesion molecule-1 expression in human 
      synovial fibroblasts.
PG  - e49999
LID - 10.1371/journal.pone.0049999 [doi]
LID - e49999
AB  - BACKGROUND: Chemokine ligand 2 (CCL2), also known as monocyte chemoattractant 
      protein-1 (MCP-1), belongs to the CC chemokine family that is associated with the 
      disease status and outcomes of osteoarthritis (OA). Here, we investigated the 
      intracellular signaling pathways involved in CCL2-induced vascular cell adhesion 
      molecule-1 (VCAM-1) expression in human OA synovial fibroblasts (OASFs). 
      METHODOLOGY/PRINCIPAL FINDINGS: Stimulation of OASFs with CCL2 induced VCAM-1 
      expression. CCL2-mediated VCAM-1 expression was attenuated by CCR2 inhibitor 
      (RS102895), PKCdelta inhibitor (rottlerin), p38MAPK inhibitor (SB203580), and AP-1 
      inhibitors (curcumin and tanshinone IIA). Stimulation of cells with CCL2 
      increased PKCdelta and p38MAPK activation. Treatment of OASFs with CCL2 also 
      increased the c-Jun phosphorylation and c-Jun binding to the AP-1 element on the 
      VCAM-1 promoter. Moreover, CCL2-mediated CCR2, PKCdelta, p38MAPK, and AP-1 pathway 
      promoted the adhesion of monocytes to the OASFs monolayer. 
      CONCLUSIONS/SIGNIFICANCE: Our results suggest that CCL2 increases VCAM-1 
      expression in human OASFs via the CCR2, PKCdelta, p38MAPK, c-Jun, and AP-1 signaling 
      pathway. The CCL2-induced VCAM-1 expression promoted monocytes adhesion to human 
      OASFs.
FAU - Lin, Yu-Min
AU  - Lin YM
AD  - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
FAU - Hsu, Chin-Jung
AU  - Hsu CJ
FAU - Liao, Yuan-Ya
AU  - Liao YY
FAU - Chou, Ming-Chih
AU  - Chou MC
FAU - Tang, Chih-Hsin
AU  - Tang CH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121121
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Acetophenones)
RN  - 0 (Benzopyrans)
RN  - 0 (CCL2 protein, human)
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Imidazoles)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - E29LP3ZMUH (rottlerin)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 14)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Acetophenones/pharmacology
MH  - Benzopyrans/pharmacology
MH  - Cell Adhesion/drug effects
MH  - *Chemokine CCL2/antagonists & inhibitors/metabolism
MH  - Fibroblasts/cytology/metabolism
MH  - Gene Expression Regulation/*drug effects
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Mitogen-Activated Protein Kinase 14/metabolism
MH  - *Osteoarthritis/genetics/metabolism
MH  - Pyridines/pharmacology
MH  - *Receptors, CCR2/antagonists & inhibitors/metabolism
MH  - Signal Transduction/drug effects
MH  - Synovial Fluid/cytology/metabolism
MH  - Transcription Factor AP-1/antagonists & inhibitors/metabolism
MH  - *Vascular Cell Adhesion Molecule-1/genetics/metabolism
PMC - PMC3503714
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/11/28 06:00
MHDA- 2013/06/01 06:00
PMCR- 2012/11/21
CRDT- 2012/11/28 06:00
PHST- 2012/07/13 00:00 [received]
PHST- 2012/10/15 00:00 [accepted]
PHST- 2012/11/28 06:00 [entrez]
PHST- 2012/11/28 06:00 [pubmed]
PHST- 2013/06/01 06:00 [medline]
PHST- 2012/11/21 00:00 [pmc-release]
AID - PONE-D-12-20937 [pii]
AID - 10.1371/journal.pone.0049999 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(11):e49999. doi: 10.1371/journal.pone.0049999. Epub 2012 Nov 21.