Item type: | Article | ||||
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Journal or Publication Title: | International Immunopharmacology | ||||
Publisher: | ELSEVIER SCIENCE BV | ||||
Place of Publication: | AMSTERDAM | ||||
Volume: | 35 | ||||
Page Range: | pp. 99-110 | ||||
Date: | 2016 | ||||
Institutions: | Chemistry and Pharmacy > Institut für Organische Chemie > Arbeitskreis Dr. Sabine Amslinger | ||||
Identification Number: |
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Keywords: | HEME OXYGENASE-1 INDUCTION; NITRIC-OXIDE PRODUCTION; NF-KAPPA-B; CARBON-MONOXIDE; COBALT-PROTOPORPHYRIN; ACTIVATOR PROTEIN-1; MURINE MACROPHAGES; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; GENE-EXPRESSION; Chalcone; HO-1; Inflammation; Nrf2; NF-kappa B; MAPK | ||||
Dewey Decimal Classification: | 500 Science > 540 Chemistry & allied sciences | ||||
Status: | Published | ||||
Refereed: | Yes, this version has been refereed | ||||
Created at the University of Regensburg: | Partially | ||||
Item ID: | 35008 |
Abstract
Inflammation plays a central role in the pathophysiology of many diseases. The inducible enzyme heme oxygenase-1 (HO-1) protects cells against inflammation and can be induced by electrophilic compounds like the chalcones (1,3-diphenylprop-2-enones) from the class of alpha,beta-unsaturated carbonyl compounds. We hypothesized that the synthetic chalcone ...

Abstract
Inflammation plays a central role in the pathophysiology of many diseases. The inducible enzyme heme oxygenase-1 (HO-1) protects cells against inflammation and can be induced by electrophilic compounds like the chalcones (1,3-diphenylprop-2-enones) from the class of alpha,beta-unsaturated carbonyl compounds. We hypothesized that the synthetic chalcone E-alpha-(p-methoxyphenyl)-2',3,4,4'-tetramethoxychalcone (E-alpha-p-OMe-C6H4-TMC) exerts anti-inflammatory effects in RAW264.7, Jurkat lymphocytes and HK-2 cells via HO-1 induction. RAW264.7 cells were treated with lipopolysaccharide prior to E-alpha-p-OMe-C6H4-TMC treatment. Subsequently, HO-1 protein induction and activity were analyzed, as well as expression of pro- and anti-inflammatory mediators, transcription factors and mitogen-activated protein kinases to evaluate the possible molecular mechanism. These results were confirmed in human cell lines (Jurkat T-lymphocytes and HK-2 epithelial cells). We found that the E-alpha-p-OMe-C6H4-TMC exerts significant anti-inflammatory effects in a dose dependent manner, showing no toxic effects in LPS-treated RAW264.7 macrophages. E-alpha-p-OMe-C6H4-TMC induced HO-1 and SOD-1 protein expression and HO-1 enzyme activity, reduced the upregulation of COX-2 and 1NOS, while inducing the translocation of Nrf2. NF-kappa B activity was attenuated following E-alpha-p-OMe-C6H4-TMC treatment accompanied by the downregulation of proinflammatory cytokines IL-1 beta, IL-6 and MCP-1. Pretreatment with E-alpha-p-OMe-C6H4-TMC revealed significant changes in phosphorylation of ERK and p38, but not JNK. These anti-inflammatory effects of E-alpha-p-OMe-C6H4-TMC were approved in Jurkat and HK-2 cells, furthermore revealing a downregulation of IL-8 and IL-10. In conclusion, it is tempting to speculate about E-alpha-p-OMe-C6H4-TMC as a new and non-toxic agent, inducing HO-1 in cells. This opens up new opportunities regarding the development of therapeutic agents using beneficial effects of HO-1 and its products. (C) 2016 Elsevier B.V. All rights reserved.
Metadata last modified: 28 May 2018 06:53