The goal of the Diindolylmethane Immune Activation Data Center is to provide a detailed overview of Diindolylmethane's immune activating properties for physicians, biomedical investigators and consumers. Diindolylmethane is a naturally occurring compound within Brassica vegetables (broccoli, cauliflower, cabbage, kale, Brussels sprouts) currently under investigation as a therapeutic for cancer, viral infections, bacterial infections and immune deficiency diseases.
Diindolylmethane (DIM) Immune Modulating Properties Include:
Stimulation of Interferon-γ Sensitivity by Increasing IFN-γ Receptors
Stimulation of Interferon-γ, G-CSF, IL-6 and IL-12 Production
Synergy with Interferon-γ in Expression of the MHC-I Complex
DIM is currently used as a treatment for Recurring Respiratory Papillomatosis and is in Phase III clinical trials for Cervical Dysplasia (both caused by HPV) at dietary supplemental dosages. Immune modulation through IFN-GR induction appears to be the only mode of action that can possibly explain this activity at such low dosages.
Diindolylmethane is the only molecule known in the biomedical field that has direct anti-cancer properties and immune modulating properties.
3,3′-Diindolylmethane stimulates murine immune function in vitro and in vivo, Xue L, Pestka J, Maoxiang L, Firestone GL, Bjeldanes LF, Journal of Nutritional Biochemistry, published online, 8-20-07. Department of Nutritional Sciences and Toxicology, University of California, Berkeley, 94720-3104, USA.
3,3′-Diindolylmethane (DIM), a major condensation product of indole-3-carbinol, exhibits chemopreventive properties in animal models of cancer. Recent studies have shown that DIM stimulates interferon-gamma (IFN-γ) production and potentiates the IFN-γ signaling pathway in human breast cancer cells via a mechanism that includes increased expression of the IFN-γ receptor. The goal of this study was to test the hypothesis that DIM modulates the murine immune function. Specifically, the effects of DIM were evaluated in a panel of murine immune function tests that included splenocyte proliferation, reactive oxygen species (ROS) generation, cytokine production and resistance to viral infection. DIM was found to induce proliferation of splenocytes as well as augment mitogen- and interleukin (IL)-2-induced splenocyte proliferation. DIM also stimulated the production of ROS by murine peritoneal macrophage cultures. Oral administration of DIM, but not intraperitoneal injection, induced elevation of serum cytokines in mice, including IL-6, granulocyte colony-stimulating factor (G-CSF), IL-12 and IFN-γ. Finally, in a model of enteric virus infection, oral DIM administration to mice enhanced both clearance of reovirus from the GI tract and the subsequent mucosal IgA response. Thus, DIM is a potent stimulator of immune function. This property might contribute to the cancer inhibitory effects of this indole.
Activation and potentiation of interferon-gamma signaling by 3,3'-diindolylmethane in MCF-7 breast cancer cells. Riby JE, Xue L, Chatterji U, Bjeldanes EL, Firestone GL, Bjeldanes LF. Department of Nutritional Sciences and Toxicology, University of California, Berkeley, 94720-3104, USA. Molecular Pharmacology. 2006 Feb;69(2):430-9.
3,3'-Diindolylmethane (DIM), a natural autolytic product in plants of the
Brassica genus, including broccoli, cauliflower, and Brussels sprouts,
exhibits promising cancer protective activities, especially against mammary
neoplasia in animal models. We observed previously that DIM induced a G(1)
cell-cycle arrest and strong induction of cell-cycle inhibitor p21
expression and promoter activity in both estrogen-responsive and
-independent breast cancer cell lines. We showed recently that DIM
up-regulates the expression of interferon gamma (IFNgamma) in human MCF-7
breast cancer cells. This novel effect may contribute to the anticancer
effects of DIM because IFNgamma plays an important role in preventing the
development of primary and transplanted tumors. In this study, we observed
that DIM activated the IFNgamma signaling pathway in human breast cancer
cells. DIM activated the expression of the IFNgamma receptor (IFNGR1) and
IFNgamma-responsive genes p56- and p69-oligoadenylate synthase (OAS). In
cotreatments with IFNgamma, DIM produced an additive activation of
endogenous p69-OAS and of an OAS-Luc reporter and a synergistic activation
of a GAS-Luc reporter. DIM synergistically augmented the IFNgamma induced
phosphorylation of signal transducer and activator of transcription factor
1, further evidence of DIM activation of the IFNgamma pathway. DIM and
IFNgamma produced an additive inhibition of cell proliferation and a
synergistic increase in levels of major histocompatibility complex class-1
(MHC-1) expression, accompanied by increased levels of mRNAs of
MHC-1-associated proteins and transporters. These results reveal novel
immune activating and potentiating activities of DIM in human tumor cells
that may contribute to the established effectiveness of this dietary indole
against various tumor types.
DIM stimulates IFNgamma gene expression in human breast cancer cells via the specific activation of JNK and p38 pathways. Xue L, Firestone GL, Bjeldanes LF. Department of Nutritional Sciences and Toxicology, University of California, 119 Morgan Hall, Berkeley, CA 94720-3104, USA. Oncogene. 2005 Mar 31;24(14):2343-53.
3,3'-Diindolylmethane (DIM) is a promising anticancer agent derived from Brassica vegetables, but the mechanisms of DIM action are largely unknown. We have shown that DIM can upregulate the expression and stimulate the secretion of interferon-gamma (IFNgamma) in the human MCF-7 breast cancer cell line. This novel effect may provide important clues to explain the anticancer effects of DIM because it is well known that IFNgamma plays an important role in preventing the development of primary and transplanted tumors. Utilizing promoter deletions, we show here that the region between -108 and -36 bp in the IFNgamma promoter, which contains two conserved and essential regulatory elements, is required for DIM-induced IFNgamma expression. DIM activates both JNK and p38 pathways, induces the phosphorylation of c-Jun and ATF-2, and increases the binding of the homodimer or heterodimer of c-Jun/ATF-2 to the proximal AP-1.CREB-ATF-binding element. Moreover, studies with specific enzyme inhibitors showed that up-stream Ca2+-dependent kinase(s) is required for the inducing effects of DIM in MCF-7 cells. These results establish that DIM-induced IFNgamma expression in human breast tumor cells is mediated by activation of both JNK and p38 pathways, which is ultimately dependent on intracellular calcium signaling.
DIM In-Vivo Affect on Key Immune Modulating Cytokines
In this study DIM was administered orally at 30mg/kg of body weight.
DIM In-Vivo Anti-Viral Activity Through Immune Modulation
Detailed Data Overview from the Referenced Papers:
Because of these properties, DIM is currently sold as an immune enhancing supplement: www.ActivaMune.com.
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