title: Antiinflammation effect of human placental multipotent mesenchymal stromal cells is mediated by prostaglandin E2 via a myeloid differentiation primary response gene 88-dependent pathway.
abstract: BACKGROUND
  We sought to elucidate the antiinflammation effect of human placental multipotent mesenchymal stromal cells (hPMSCs) and the possible molecular mechanisms.
  
  
  METHODS
  Immortalized murine macrophages (RAW264.7 cells), with or without hPMSCs coincubation, were treated with endotoxin to induce expression of the relevant molecules.
  
  
  RESULTS
  The peak concentrations (means ± SD) of inflammatory molecules in endotoxin-activated macrophages with hPMSCs coincubation were significantly lower than those in endotoxin-activated macrophages without hPMSCs coincubation (tumor necrosis factor-α: 9.4±0.8 vs. 13.0±1.1 ng/ml; interleukin-6: 0.8±0.1 vs. 1.2±0.1 ng/ml; macrophage inflammatory protein-2: 345±30 vs. 666±51 ng/ml; intercellular adhesion molecule 1: 1.4±0.1 vs. 1.7±0.1 ng/ml; prostaglandin E2: 5.7±0.3 vs. 8.5±0.6 ng/ml; all P<0.008). Data of the activation of nuclear factor-κB and mitogen-activated protein kinases as well as the interaction between toll-like receptor 4 and myeloid differentiation primary response gene 88 paralleled those of the inflammatory molecules. In contrast, the endotoxin binding and toll-like receptor 4/myeloid differential-2 complex activation in endotoxin-activated macrophages with hPMSCs coincubation were comparable with those in endotoxin-activated macrophages without hPMSCs coincubation. As our data revealed that hPMSCs could induce low-grade prostaglandin E2 expression in macrophages, we also employed the selective cyclooxygenase-2 inhibitor NS-398 to further elucidate the possible role of prostaglandin E2. Our data revealed that the above-mentioned hPMSC-triggered inhibitory effects were significantly reversed by NS-398.
  
  
  CONCLUSIONS
  The antiinflammation effect of human placental multipotent mesenchymal stromal cells is mediated, at least in part, by prostaglandin E2 via a myeloid differentiation primary response gene 88-dependent pathway.
authors: Division of High Risk Pregnancy, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, and Graduate Institute of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan.
authors: Chie-Pein
authors: CP
authors: Chen
authors: Pei-Shan
authors: PS
authors: Tsai
authors: Chun-Jen
authors: CJ
authors: Huang
mesh_terms: D000818:Animals; D002450:Cell Communication; D002478:Cells, Cultured; D015232:Dinoprostone / Q000502:physiology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D016753:Interleukin-10 / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D051218:Lymphocyte Antigen 96 / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000502:physiology*; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone