PMID- 22848642
OWN - NLM
STAT- MEDLINE
DCOM- 20130110
LR  - 20240318
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 7
DP  - 2012
TI  - Monocyte chemoattractant protein-1 secreted by decidual stromal cells inhibits NK 
      cells cytotoxicity by up-regulating expression of SOCS3.
PG  - e41869
LID - 10.1371/journal.pone.0041869 [doi]
LID - e41869
AB  - BACKGROUND: Decidual stromal cells (DSCs) are of particular importance due to 
      their pleiotropic functions during pregnancy. Although previous research has 
      demonstrated that DSCs participated in the regulation of immune cells during 
      pregnancy, the crosstalk between DSCs and NK cells has not been fully elucidated. 
      To address this issue, we investigated the effect of DSCs on perforin expression 
      in CD56(+) NK cells and explored the underlying mechanism. METHODOLOGY/PRINCIPAL 
      FINDINGS: Flow cytometry analysis showed perforin production in NK cells was 
      attenuated by DSC media, and it was further suppressed by media from DSCs 
      pretreated with lipopolysaccharide (LPS). However, the expression of granzyme A 
      and apoptosis of NK cells were not influenced by DSC media. ELISA assays to 
      detect cytokine production indicated that monocyte chemoattractant protein-1 
      (MCP-1) in the supernatant of DSCs conditioned culture significantly increased 
      after LPS stimulation. The inhibitory effect of DSC media on perforin was 
      abolished by the administration of anti-MCP-1 neutralizing antibody. Notably, 
      reduced perforin expression attenuated the cytotoxic potential of CD56(+) NK 
      cells to K562 cells. Moreover, Suppressor of cytokine signaling 3 (SOCS3) 
      expression in NK cells was enhanced by treatment with MCP-1, as measured by 
      RT-PCR and western blot. Interestingly, MCP-1-induced perforin expression was 
      partly abolished by the siRNA induced SOCS3 knockdown. Western blot analysis 
      suggested that both NF-kappaB and ERK/MAPKs pathway were involved in the LPS-induced 
      upregulation of MCP-1 in DSCs. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate 
      that LPS induces upregulation of MCP-1 in DSCs, which may play a critical role in 
      inhibiting the cytotoxicity of NK cells partly by promoting SOCS3 expression. 
      These findings suggest that the crosstalk between DSCs and NK cells may be 
      crucial to maintain pregnancy homeostasis.
FAU - Xu, Xiaofei
AU  - Xu X
AD  - Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, 
      Jinan, Shandong, China.
FAU - Wang, Qingjie
AU  - Wang Q
FAU - Deng, Biping
AU  - Deng B
FAU - Wang, Huayang
AU  - Wang H
FAU - Dong, Zhaogang
AU  - Dong Z
FAU - Qu, Xun
AU  - Qu X
FAU - Kong, Beihua
AU  - Kong B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120727
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CD56 Antigen)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (SOCS3 protein, human)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 126465-35-8 (Perforin)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.4.21.- (Granzymes)
SB  - IM
MH  - Apoptosis/drug effects
MH  - CD56 Antigen/metabolism
MH  - Chemokine CCL2/biosynthesis/genetics/*metabolism
MH  - Culture Media, Conditioned/metabolism
MH  - Decidua/*cytology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Female
MH  - Granzymes/metabolism
MH  - Humans
MH  - Killer Cells, Natural/*cytology/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - MAP Kinase Signaling System/drug effects
MH  - NF-kappa B/metabolism
MH  - Perforin/biosynthesis/metabolism
MH  - Pregnancy
MH  - Pregnancy Trimester, First
MH  - RNA, Messenger/genetics/metabolism
MH  - Stromal Cells/cytology/drug effects/*metabolism
MH  - Suppressor of Cytokine Signaling 3 Protein
MH  - Suppressor of Cytokine Signaling Proteins/genetics/*metabolism
MH  - *Up-Regulation/drug effects
PMC - PMC3407114
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/08/01 06:00
MHDA- 2013/01/11 06:00
PMCR- 2012/07/27
CRDT- 2012/08/01 06:00
PHST- 2012/03/01 00:00 [received]
PHST- 2012/06/29 00:00 [accepted]
PHST- 2012/08/01 06:00 [entrez]
PHST- 2012/08/01 06:00 [pubmed]
PHST- 2013/01/11 06:00 [medline]
PHST- 2012/07/27 00:00 [pmc-release]
AID - PONE-D-11-08927 [pii]
AID - 10.1371/journal.pone.0041869 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(7):e41869. doi: 10.1371/journal.pone.0041869. Epub 2012 Jul 27.