Antiinflammation Effect of Human Placental Multipotent Mesenchymal Stromal Cells Is Mediated by Prostaglandin E2 via a Myeloid Differentiation Primary Response Gene 88-dependent Pathway

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-alpha : 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 E-2: 5.7 +/- 0.3 vs. 8.5 +/- 0.6 ng/ml; all P < 0.008). Data of the activation of nuclear factor-kappa B 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 E-2 expression in macrophages, we also employed the selective cyclooxygenase-2 inhibitor NS-398 to further elucidate the possible role of prostaglandin E-2. 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 E-2 via a myeloid differentiation primary response gene 88-dependent pathway.