15-deoxy-Δ12,14-prostaglandin J2 Down-Regulates Activin-Induced Activin Receptor, Smad, and Cytokines Expression via Suppression of NF-κB and MAPK Signaling in HepG2 Cells
15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and activin are implicated in the control of apoptosis, cell proliferation, and inflammation in cells. We examined both the mechanism by which 15d-PGJ2 regulates the transcription of activin-induced activin receptors (ActR) and Smads in HepG2 cells and the...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2013/751261 |
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| author | Seung-Won Park Chunghee Cho Byung-Nam Cho Youngchul Kim Tae Won Goo Young Il Kim |
| author_facet | Seung-Won Park Chunghee Cho Byung-Nam Cho Youngchul Kim Tae Won Goo Young Il Kim |
| author_sort | Seung-Won Park |
| collection | DOAJ |
| description | 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and activin are implicated in the control of apoptosis, cell proliferation, and inflammation in cells. We examined both the mechanism by which 15d-PGJ2 regulates the transcription of activin-induced activin receptors (ActR) and Smads in HepG2 cells and the involvement of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways in this regulation. Activin A (25 ng/mL) inhibited HepG2 cell proliferation, whereas 15d-PGJ2 (2 μM and 5 μM) had no effect. Activin A and 15d-PGJ2 showed different regulatory effects on ActR and Smad expression, NF-κB p65 activity and MEK/ERK phosphorylation, whereas they both decreased IL-6 production and increased IL-8 production. When co-stimulated with 15d-PGJ2 and activin, 15d-PGJ2 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-PGJ2 inhibited activin-induced NF-κB p65 activity and activin-induced MEK/ERK phosphorylation. These results suggest that 15d-PGJ2 suppresses activin-induced ActR and Smad expression, down-regulates IL-6 production, and up-regulates IL-8 production via suppression of NF-κB and MAPK signaling pathway in HepG2 cells. Regulation of ActR and Smad transcript expression and cytokine production involves NF-κB and the MAPK pathway via interaction with 15d-PGJ2/activin/Smad signaling. |
| format | Article |
| id | doaj-art-38ccde9e454a4e77a8c78053420f2cd6 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-38ccde9e454a4e77a8c78053420f2cd62025-08-20T03:55:11ZengWileyPPAR Research1687-47571687-47652013-01-01201310.1155/2013/75126175126115-deoxy-Δ12,14-prostaglandin J2 Down-Regulates Activin-Induced Activin Receptor, Smad, and Cytokines Expression via Suppression of NF-κB and MAPK Signaling in HepG2 CellsSeung-Won Park0Chunghee Cho1Byung-Nam Cho2Youngchul Kim3Tae Won Goo4Young Il Kim5Department of Biotechnology, Catholic University of Daegu, Daegu 712-702, Republic of KoreaSchool of Life Science, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, Republic of KoreaDepartment of Life Sciences, The Catholic University of Korea, Bucheon 420-743, Republic of KoreaDepartment of Internal Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130-872, Republic of KoreaDepartment of Agricultural Biology, National Academy of Agricultural Science, RDA, Suwon 441-100, Republic of KoreaMedical Science Research Institute, Kyung Hee University Medical Center, Seoul 130-872, Republic of Korea15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and activin are implicated in the control of apoptosis, cell proliferation, and inflammation in cells. We examined both the mechanism by which 15d-PGJ2 regulates the transcription of activin-induced activin receptors (ActR) and Smads in HepG2 cells and the involvement of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways in this regulation. Activin A (25 ng/mL) inhibited HepG2 cell proliferation, whereas 15d-PGJ2 (2 μM and 5 μM) had no effect. Activin A and 15d-PGJ2 showed different regulatory effects on ActR and Smad expression, NF-κB p65 activity and MEK/ERK phosphorylation, whereas they both decreased IL-6 production and increased IL-8 production. When co-stimulated with 15d-PGJ2 and activin, 15d-PGJ2 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-PGJ2 inhibited activin-induced NF-κB p65 activity and activin-induced MEK/ERK phosphorylation. These results suggest that 15d-PGJ2 suppresses activin-induced ActR and Smad expression, down-regulates IL-6 production, and up-regulates IL-8 production via suppression of NF-κB and MAPK signaling pathway in HepG2 cells. Regulation of ActR and Smad transcript expression and cytokine production involves NF-κB and the MAPK pathway via interaction with 15d-PGJ2/activin/Smad signaling.http://dx.doi.org/10.1155/2013/751261 |
| spellingShingle | Seung-Won Park Chunghee Cho Byung-Nam Cho Youngchul Kim Tae Won Goo Young Il Kim 15-deoxy-Δ12,14-prostaglandin J2 Down-Regulates Activin-Induced Activin Receptor, Smad, and Cytokines Expression via Suppression of NF-κB and MAPK Signaling in HepG2 Cells PPAR Research |
| title | 15-deoxy-Δ12,14-prostaglandin J2 Down-Regulates Activin-Induced Activin Receptor, Smad, and Cytokines Expression via Suppression of NF-κB and MAPK Signaling in HepG2 Cells |
| title_full | 15-deoxy-Δ12,14-prostaglandin J2 Down-Regulates Activin-Induced Activin Receptor, Smad, and Cytokines Expression via Suppression of NF-κB and MAPK Signaling in HepG2 Cells |
| title_fullStr | 15-deoxy-Δ12,14-prostaglandin J2 Down-Regulates Activin-Induced Activin Receptor, Smad, and Cytokines Expression via Suppression of NF-κB and MAPK Signaling in HepG2 Cells |
| title_full_unstemmed | 15-deoxy-Δ12,14-prostaglandin J2 Down-Regulates Activin-Induced Activin Receptor, Smad, and Cytokines Expression via Suppression of NF-κB and MAPK Signaling in HepG2 Cells |
| title_short | 15-deoxy-Δ12,14-prostaglandin J2 Down-Regulates Activin-Induced Activin Receptor, Smad, and Cytokines Expression via Suppression of NF-κB and MAPK Signaling in HepG2 Cells |
| title_sort | 15 deoxy δ12 14 prostaglandin j2 down regulates activin induced activin receptor smad and cytokines expression via suppression of nf κb and mapk signaling in hepg2 cells |
| url | http://dx.doi.org/10.1155/2013/751261 |
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