A Novel Peroxisome Proliferator-activated Receptor (PPAR)γ Agonist 2-Hydroxyethyl 5-chloro-4,5-didehydrojasmonate Exerts Anti-Inflammatory Effects in Colitis
| Autor: | Hyung Ryong Moon, Eunok Im, Sujin Son, Yunna Lee, Jieun Choo, Jee H. Jung, Charalabos Pothoulakis, Xin-jia Yan, Seong Jin Kim, Tae Hwan Noh |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Biochemistry & Molecular Biology Chemokine Transcription Genetic mitogen-activated protein kinase colitis medicine.medical_treatment Anti-Inflammatory Agents Peroxisome proliferator-activated receptor Cyclopentanes Pharmacology Inbred C57BL Medical and Health Sciences Biochemistry Cell Line Mice Genetic inflammatory bowel disease cytokine medicine Animals Oxylipins CX3CL1 Receptor Molecular Biology chemistry.chemical_classification peroxisome proliferator-activated receptor biology NF-kappa B Molecular Bases of Disease Cell Biology Biological Sciences Colitis Mice Inbred C57BL PPAR gamma Cytokine CXCL3 chemistry Chemical Sciences Immunology biology.protein Signal transduction Rosiglitazone Transcription medicine.drug |
| Zdroj: | The Journal of biological chemistry, vol 290, iss 42 Choo, J; Lee, Y; Yan, XJ; Noh, TH; Kim, SJ; Son, S; et al.(2015). A Novel Peroxisome Proliferator-activated Receptor (PPAR)y Agonist 2-Hydroxyethyl 5-chloro-4, 5-didehydrojasmonate Exerts Anti-Inflammatory Effects in Colitis. Journal of Biological Chemistry, 290(42), 25609-25619. doi: 10.1074/jbc.M115.673046. UCLA: Retrieved from: http://www.escholarship.org/uc/item/3038w8kf |
| ISSN: | 0021-9258 |
| Popis: | © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Inflammatory bowel disease (IBD) is a chronic inflammatory disease with increasing incidence and prevalence worldwide. Here we investigated the newly synthesized jasmonate analogue 2-hydroxyethyl 5-chloro-4, 5-didehydrojasmonate (J11-Cl) for its anti-inflammatory effects on intestinal inflammation. First, to test whether J11-Cl can activate peroxisome proliferator-activated receptors (PPARs), we performed docking simulations because J11-Cl has a structural similarity with anti-inflammatory 15-deoxy-Δ12,14-prostaglandin J2(15d-PGJ2), one of the endogenous ligands of PPARy. J11-Cl bound to the ligand binding domain of PPARy in the same manner as 15d-PGJ2and rosiglitazone, and significantly increased transcriptional activity of PPARγ. In animal experiments, colitis was significantly reduced in mice with J11-Cl treatment, determined by analyses of survival rate, body weight changes, clinical symptoms, and histological evaluation. Moreover, J11-Cl decreased production of pro-inflammatory cytokines including IL-6, IL-8, and G-CSF as well as chemokines including chemokine (C-C motif) ligand (CCL)20, chemokine (C-X-C motif) ligand (CXCL)2, CXCL3, and chemokine (C-X3-C motif) ligand 1 (CX3CL1) in colon tissues, and LPS or TNF-α-stimulated macrophages and epithelial cells. In contrast, production of anti-inflammatory cytokines including IL-2 and IL-4 as well as the proliferative factor, GM-CSF, was increased by J11-Cl. Furthermore, inhibition of MAPKs and NF-κB activation by J11-Cl was also observed. J11-Cl reduced intestinal inflammation by increasing the transcriptional activity of PPARγ and modulating inflammatory signaling pathways. Therefore, our study suggests that J11-Cl may serve as a novel therapeutic agent against IBD. |
| Databáze: | OpenAIRE |
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