NF-kappaB decoy oligonucleotides suppress RANTES expression and monocyte chemotactic activity via NF-kappaB inactivation in stromal cells of ectopic endometrium.

Autor: Xiu-li W; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, 368 North-Jiangdong Road, Nanjing, China. xiuli_2266@163.com, Su-ping H, Hui-hua D, Zhi-xue Y, Shi-long F, Pin-hong L
Jazyk: angličtina
Zdroj: Journal of clinical immunology [J Clin Immunol] 2009 May; Vol. 29 (3), pp. 387-95. Date of Electronic Publication: 2009 Jan 27.
DOI: 10.1007/s10875-009-9274-z
Abstrakt: Background: The nuclear factor kappa B (NF-kappaB) 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-kappaB decoy oligonucleotides (ODNs) on NF-kappaB 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)-1beta. Four hours after transfection of NF-kappaB decoy ODNs, 10 ng/ml IL-1beta was added to induce the ectopic endometrial stromal cells to secrete RANTES. The NF-kappaB 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-1beta induced significantly higher levels (P < 0.05) of RANTES expression in a time-dependent manner in ectopic endometrial stromal cells compared with IL-1beta-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-kappaB decoy ODNs dramatically decreased (P < 0.05) the NF-kappaB activation, RANTES expression, and monocyte chemotactic activity in IL-1beta-induced ectopic endometrial stromal cells.
Conclusions: NF-kappaB decoy ODNs may exert anti-inflammatory effects in ectopic endometrial stromal cells via the suppression of NF-kappaB activation, RANTES expression, and monocyte chemotactic activity.
Databáze: MEDLINE