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.