15-deoxy- Δ-prostaglandin J down-regulates activin-induced activin receptor,smad,and cytokines expression via suppression of NF- B and MAPK signaling in HepG2 Cells

15-deoxy- δ 12,14 -prostaglandin j(15d-pgj and activin are implicated in the control of apoptosis,cell proliferation,and inflammation in cells. we examined both the mechanism by which 15d-pgjregulates the transcription of activin-induced activin receptors (actr) and smads in hepg2 cells and the involvement of the nuclear factor-b (nf-b) and mitogen-activated protein kinase (mapk) pathways in this regulation. activin a (25 ng/ml) inhibited hepg2 cell proliferation,whereas 15d-pgj(2 m and 5 m) had no effect. activin a and 15d-pgjshowed different regulatory effects on actr and smad expression,nf-b p65 activity and mek/erk phosphorylation,whereas they both decreased il-6 production and increased il-8 production. when co-stimulated with 15d-pgjand activin,15d-pgjinhibited the activin-induced increases in actr and smad expression,and decreased activin-induced il-6 production. however,it increased activin-induced il-8 production. in addition,15d-pgjinhibited activin-induced nf-b p65 activity and activin-induced mek/erk phosphorylation. these results suggest that 15d-pgjsuppresses activin-induced actr and smad expression,down-regulates il-6 production,and up-regulates il-8 production via suppression of nf-b and mapk signaling pathway in hepg2 cells. regulation of actr and smad transcript expression and cytokine production involves nf-b and the mapk pathway via interaction with 15d-pgjactivin/smad signaling. © 2013 seung-won park et al.