(E)-2-Methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol attenuates PMA-induced inflammatory responses in human monocytic cells through PKCδ/JNK/AP-1 pathways.

Abstract

(E)-2-Methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP), a new (E)-2,4-bis(p-hydroxyphenyl)-2 - butenal derivative, reportedly has therapeutic effects such as anti-arthritic properties. Although previous studies showed that MMPP has anti-arthritic effects on rheumatoid arthritis (RA), the anti-inflammation mechanism of MMPP remains unclear. In this study, phorbol-12-myristate 13-acetate (PMA) was used as an inflammatory stimulus to evaluate the detailed mechanism of the MMPP-mediated anti-inflammatory effect in human monocytic THP-1 cells. We investigated the effects of MMPP on inflammation-related pathways including protein kinase Cδ (PKCδ), mitogen-activated protein kinase, and activator protein-1 (AP-1). PMA induced the translocation of PKCs from the cytosol to the membrane and phosphorylated JNK. MMPP inhibited PMA-induced membrane translocation of PKCδ, phosphorylation of JNK, and nuclear translocation of AP-1, resulting in downregulation of cyclooxygenase-2 and chemokine ligand 5 production. These findings indicate that MMPP inhibits inflammatory responses in THP-1 cells by mitigating PMA-induced activation of PKCδ and JNK and nuclear translocation of AP-1. Therefore, MMPP may be useful as an anti-inflammatory drug.

• Authors: Soo-Jin Kim, Yong-Seok Song, Thu-Huyen Pham, Yesol Bak, Hee-Pom Lee, Jin-Tae Hong, Do-Young Yoon
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 825 Pg. 19-27 (Apr 15 2018) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 29371085 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Phthalic Acids
• Polymethacrylic Acids
• Transcription Factor AP-1
• poly(MPC-co-MA)
• Phosphorylcholine
• Cyclooxygenase 2
• Protein Kinase C-delta
• Mitogen-Activated Protein Kinases
• Tetradecanoylphorbol Acetate
• magnesium monoperoxyphthalate

Topics

• Anti-Inflammatory Agents (pharmacology)
• Cell Line
• Cyclooxygenase 2 (metabolism)
• Down-Regulation (drug effects)
• Humans
• Inflammation (chemically induced, drug therapy)
• MAP Kinase Signaling System (drug effects)
• Mitogen-Activated Protein Kinases (metabolism)
• Monocytes (drug effects, metabolism)
• Phosphorylcholine (analogs & derivatives, pharmacology)
• Phthalic Acids (pharmacology)
• Polymethacrylic Acids (pharmacology)
• Protein Kinase C-delta (metabolism)
• Signal Transduction (drug effects)
• Tetradecanoylphorbol Acetate (metabolism)
• Transcription Factor AP-1 (metabolism)