Estrogen receptor β agonist diarylpropionitrile inhibits lipopolysaccharide-induced regulated on activation normal T cell expressed and secreted (RANTES) production in macrophages by repressing nuclear factor κb activation

摘要

Objective: To investigate the effect of the estrogen receptor-β (ERβ) agonist diarylpropionitrile (DPN) on lipopolysaccharide (LPS)-induced regulated on activation normal T cell expressed and secreted (RANTES) production in macrophages and the possible mechanisms. Design: Cellular and molecular biology experimental study. Setting: University-based research laboratory. Patient(s): None. Intervention(s): ERβ mRNA and protein expression determined in murine macrophage cell line RAW264.7 cells using reverse-transcription polymerase chain reaction and Western blot analysis; RANTES production detected by ELISA in LPS-stimulated RAW264.7 cells and ERβ knockdown RAW264.7 cells after the addition of DPN, phosphorylation of p65 and IκB degradation detected by Western blot analysis; and nuclear accumulation of p65 visualized using immunofluorescence. Main Outcome Measure(s): LPS-induced RANTES production and phosphorylation of p65 and IκB. Result(s): ERβ was expressed in RAW264.7 cells, and DPN statistically significantly decreased LPS-induced RANTES production in RAW264.7 cells. Small interfering RNA targeting the ERβ gene inhibited the effect of DPN on RANTES production. In addition, DPN inhibited nuclear translocation and phosphorylation of p65 by inhibiting IκB degradation and thus prohibited the activation of nuclear factor κB (NF-κB). Conclusion(s): Diarylpropionitrile down-regulates LPS-induced RANTES production via ERβ. This effect of DPN is likely due to repression of nuclear factor κB activation.