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.
|Number of pages||12|
|Publication status||Published - Sept 2012|
ASJC Scopus subject areas
- Anesthesiology and Pain Medicine