Antiinflammation Effect of Human Placental Multipotent Mesenchymal Stromal Cells Is Mediated by Prostaglandin E2via 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.