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3,3'-Diindolylmethane suppresses the inflammatory response to lipopolysaccharide in murine macrophages

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Authors
Cho, Han Jin; Seon, Mi Ra; Lee, Yeo Myeong; Kim, Jaebong; Kim, Jin-Kyung; Kim, Sang Geon; Park, Jung Han Yoon
Issue Date
2008
Publisher
American Society for Nutrition
Citation
J Nutr. 2008;138:17-23
Keywords
AnimalsAnticarcinogenic Agents/*pharmacologyCell LineDinoprostone/genetics/metabolismDose-Response Relationship, DrugGene Expression Regulation/drug effectsIndoles/*pharmacologyInflammation/immunology/*metabolismInterleukin-1/genetics/metabolismInterleukin-1beta/genetics/metabolismLipopolysaccharides/*antagonists & inhibitors/*pharmacologyMacrophages/*drug effects/immunology/metabolismMiceNitric Oxide/metabolismTumor Necrosis Factor-alpha/genetics/metabolism
Abstract
3,3'-Diindolylmethane (DIM), a major acid-condensation product of indole-3-carbinol, has been shown to have multiple anticancer effects in experimental models. Because recurrent or chronic inflammation has been implicated in the development of a variety of human cancers, this study examined the antiinflammatory effects of DIM and the underlying mechanisms using lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. DIM significantly decreased the release of nitric oxide (NO), prostaglandin (PG)E2, tumor necrosis factor alpha, interleukin (IL)-6, and IL-1beta by RAW264.7 cells treated with LPS. DIM inhibited LPS-induced increases in protein levels of inducible NO synthase (iNOS), which were accompanied by decreased iNOS mRNA levels and transcriptional activity. The mRNA levels of phospholipase A2 decreased, whereas neither cyclooxygenases-2 protein nor transcript was altered by DIM. In addition, DIM suppressed LPS-induced nuclear factor-kappaB (NF-kappaB) transcriptional activity, NF-kappaB DNA-binding activity, translocation of p65 (RelA) to the nucleus, and degradation of inhibitor of kappaB alpha. Furthermore, DIM decreased LPS-induced transcriptional activity of activator protein (AP)-1, AP-1 DNA-binding activity, and phosphorylation of stress-activated protein kinase/Jun-N-terminal kinase and c-Jun. We demonstrate that DIM inhibits LPS-induced release of proinflammatory mediators in murine macrophages. Downregulation of NF-kappaB and AP-1 signaling may be one of the mechanisms by which DIM inhibits inflammatory responses.
ISSN
1541-6100 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18156398

http://hdl.handle.net/10371/28614
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College of Medicine/School of Medicine (의과대학/대학원)Program in Clinical Pharmacology (협동과정-임상약리학전공)Journal Papers (저널논문_협동과정-임상약리학전공)
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