5-Deoxy-Δ 12,14 -Prostaglandin J 2 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 2 (15d-PGJ 2 ) and activin are implicated in the control of apoptosis, cell proliferation, and inflammation in cells. We examined both the mechanism by which 15d-PGJ 2 regulates 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 (2 M and 5 M) had no effect. Activin A and 15d-PGJ 2 showed 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 costimulated with 15d-PGJ 2 and activin, 15d-PGJ 2 inhibited 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-PGJ 2 inhibited activininduced NF-B p65 activity and activin-induced MEK/ERK phosphorylation. These results suggest that 15d-PGJ 2 suppresses 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-PGJ 2 /activin/Smad signaling
