| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Kim, Seong Jin Pothoulakis, Charalabos Jung, Jee H. Moon, Hyung Ryong Son, Sujin Choo, Jieun Im, Eunok Noh, Tae Hwan Lee, Yunna Yan, Xin-jia |
| Description |
Author Affiliation: Choo J ( From the College of Pharmacy, Pusan National University, Busan, 609-735, Korea.); Lee Y ( From the College of Pharmacy, Pusan National University, Busan, 609-735, Korea.); Yan XJ ( College of Pharmacy, Harbin University of Commerce, Harbin, Heilongjiang Province 150076, P.R. China, and.); Noh TH ( From the College of Pharmacy, Pusan National University, Busan, 609-735, Korea.); Kim SJ ( From the College of Pharmacy, Pusan National University, Busan, 609-735, Korea.); Son S ( From the College of Pharmacy, Pusan National University, Busan, 609-735, Korea.); Pothoulakis C ( Section of Inflammatory Bowel Disease & Inflammatory Bowel Disease Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095.); Moon HR ( From the College of Pharmacy, Pusan National University, Busan, 609-735, Korea.); Jung JH ( From the College of Pharmacy, Pusan National University, Busan, 609-735, Korea.); Im E ( From the College of Pharmacy, Pusan National University, Busan, 609-735, Korea, eoim@pusan.ac.kr.) |
| Abstract |
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-Δ(12,14)-prostaglandin J2 (15d-PGJ2), one of the endogenous ligands of PPARγ. J11-Cl bound to the ligand binding domain of PPARγ in the same manner as 15d-PGJ2 and 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- -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. |
| ISSN |
00219258 |
| e-ISSN |
1083351X |
| Journal |
Journal of Biological Chemistry |
| Issue Number |
42 |
| Volume Number |
290 |
| Language |
English |
| Publisher |
American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date |
2015-10-16 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Anti-Inflammatory Agents Pharmacology Colitis Prevention & Control Cyclopentanes Oxylipins PPAR Gamma Agonists Animals Chemistry Cell Line Mice Mice, Inbred C57BL Transcription, Genetic Drug Effects Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Cell Biology Biochemistry Molecular Biology |
