NF-κB Decoy Oligonucleotides Suppress RANTES Expression and Monocyte Chemotactic Activity via NF-κB Inactivation in Stromal Cells of Ectopic Endometrium

Journal of Clinical Immunology(2009)

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摘要
Background The nuclear factor kappa B (NF-κB) pathway is a critical mediator of regulated on activation, normal T cell expressed and secreted (RANTES) gene regulation and therefore represents a potential target for therapy of endometriosis-associated symptoms. Objective The objective of this study was to investigate the effect of NF-κB decoy oligonucleotides (ODNs) on NF-κB activation, RANTES expression, and monocyte chemotactic activity in ectopic endometrial stromal cells in vitro. Methods A specific sandwich enzyme-linked immunosorbent assay (ELISA) was used to quantify RANTES expression in ectopic and normal endometrial stromal cells stimulated by interleukin (IL)-1β. Four hours after transfection of NF-κB decoy ODNs, 10 ng/ml IL-1β was added to induce the ectopic endometrial stromal cells to secrete RANTES. The NF-κB activation, RANTES expression, and monocyte chemotactic activity in ectopic endometrial stromal cells were respectively evaluated by electrophoretic mobility shift assay, ELISA, and Boyden chambers. Results IL-1β induced significantly higher levels ( P < 0.05) of RANTES expression in a time-dependent manner in ectopic endometrial stromal cells compared with IL-1β-untreated ectopic and normal endometrial stromal cells. The RANTES accounts for the majority (68%) of the monocyte chemotactic activity in conditioned media of ectopic endometrial stromal cells. In vitro transfection of NF-κB decoy ODNs dramatically decreased ( P < 0.05) the NF-κB activation, RANTES expression, and monocyte chemotactic activity in IL-1β-induced ectopic endometrial stromal cells. Conclusions NF-κB decoy ODNs may exert anti-inflammatory effects in ectopic endometrial stromal cells via the suppression of NF-κB activation, RANTES expression, and monocyte chemotactic activity.
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关键词
NF-κB decoy ODNs,ectopic endometrium,RANTES,monocyte,IL-1β
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