title: Monocyte chemoattractant protein-1 secreted by decidual stromal cells inhibits NK cells cytotoxicity by up-regulating expression of SOCS3.
abstract: 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.
  
  
  RESULTS
  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-κB and ERK/MAPKs pathway were involved in the LPS-induced upregulation of MCP-1 in DSCs.
  
  
  CONCLUSIONS
  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.
authors: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors: Xiaofei
authors: X
authors: Xu
authors: Qingjie
authors: Q
authors: Wang
authors: Biping
authors: B
authors: Deng
authors: Huayang
authors: H
authors: Wang
authors: Zhaogang
authors: Z
authors: Dong
authors: Xun
authors: X
authors: Qu
authors: Beihua
authors: B
authors: Kong
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D019002:CD56 Antigen / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000378:metabolism; D003656:Decidua / Q000166:cytology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D054353:Perforin / Q000096:biosynthesis / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D019002:CD56 Antigen; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D054353:Perforin; D048049:Extracellular Signal-Regulated MAP Kinases; D053804:Granzymes