Diindolylmethane decreases Tumor Necrosis Factor Alpha

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DIM decreases TNF-α
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2008

Non-human Cells

3,3'-Diindolylmethane suppresses the inflammatory response to lipopolysaccharide in murine macrophages
Cho HJ, Kim J, Kim JK, Kim SG, Lee YM, Park JH, Seon MR
«RAW264.7 cell were plated in 100-mm dishes at 1.5 3 106 cell per dish and serum deprived as described above. After serum deprivation, cell were incubated for 18 h in DMEM containing 1% FBS with 0 or 10 mmol/L DIM. Cell were then treated with or without 100 mg/L LPS for another 12 h. Total RNA was isolated using Tri reagent (Sigma) and a cDNA microarray was performed using a mouse whole genome chip (38.5K) in GenomicTree. The RNA pooled from 3 independent experiments was used in each chip. The images from the scanned microarrays were analyzed using Agilent GeneSpringGX 7.3 software and normalized by the intensity dependent (LOWESS) normalization method. The microarrays were performed by comparing the gene expression of each treatment group (10 mmol/L DIM, 100 mg/L LPS, or LPS 1 DIM) with that of the control group (0 mmol/L DIM) and the fold changes in gene expression by LPS, LPS 1 DIM, or DIM relative to the control are listed. »

«To evaluate changes in gene expression following treatment with LPS and DIM, cDNA microarrays were performed using a mouse whole genome chip (38.5K). A total of 2294 genes were found to be induced at least 2-fold by LPS, from which we chose inflammation and immune-like response related genes. Among these genes, those down-regulated by DIM are listed in Supplemental Table 1. LPS dramatically increased gene expression of pro-inflammatory cytokine such as TNFa (TNF-α), IL-1b, and IL-6, and chemokine ligands. This increased expression was substantially suppressed by DIM treatment. DIM inhibited LPS-induced gene expression of iNOS, whereas DIM had no effect on COX-2 gene expression. These results are consistent with the results shown in Figure 1 obtained with western blot and RT-PCR analysis showing that DIM decreased protein and mRNA levels of iNOS but not those of COX-2. Expression of PLA2 gene was increased by LPS, an effect mitigated by DIM treatment.
Organism: In vitro
Notable Magnitude of Effect.
#Animals, Anticarcinogenic Agents / pharmacology*, Cell Line, Dinoprostone / genetics, Dinoprostone / metabolism, Dose-Response Relationship, Drug, Gene Expression Regulation / drug effects, Han Jin Cho, Indoles / pharmacology*, Inflammation / immunology, Inflammation / metabolism*, Interleukin-1 / genetics, Interleukin-1 / metabolism, Interleukin-1beta / genetics, Interleukin-1beta / metabolism, Jung Han Yoon Park, Lipopolysaccharides / antagonists &, Lipopolysaccharides / pharmacology*, MEDLINE, Macrophages / drug effects*, Macrophages / immunology, Macrophages / metabolism, Mi Ra Seon, Mice, NCBI, NIH, NLM, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, Nitric Oxide / metabolism, Non-U.S. Gov', PubMed Abstract, Research Support, Tumor Necrosis Factor-alpha / genetics, Tumor Necrosis Factor-alpha / metabolism, doi:10.1093/jn/138.1.17, inhibitors*, pmid:18156398more...
pubmed.ncbi.nlm.nih.gov/18156398
10.1093/jn/138.1.17

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DIM decreases TNF-α
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