Abstract
Aim To investigate the potential molecular mechanism of paeoniflorin(Pae) in inhibiting PGE2 induced rat fibroblast-like synoviocytes(FLSs) hyperplasy.Methods Rat FLSs were cultured in the presence of prostaglandin E2(PGE2) with or without different concentrations of Pae.FLSs proliferations were determined by 3H-TdR incorporation assay.Cyclic adenosine monophosphate(cAMP) levels in synoviocytes were assessed by radioimmunoassay(RIA).The expressions of EP2 and β-arrestin 2 in whole FLSs or on membrane were measured by Western blot or flow cytometry.Results Pae significantly inhibited rat FLS proliferation induced by PGE2 via increasing cAMP levels.High levels of total EP2,β-arrestin 2 and membrane β-arrestin 2 expression in FLSs induced by PGE2 were decreased by different concentrations of Pae administration.EP2 was downregulated on FLSs membrane after PGE2 stimulation;however,was restored by Pae in various degrees.Conclusions Our findings suggest that Pae inhibits rat FLSs proliferation induced by PGE2 via arresting EP2 receptor internalization by inhibiting β-arrestin 2 recruit to cell membrane.
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