Suppression of inflammation-associated factors by indole-3-carbinol in mice fed high-fat diets and in isolated, co-cultured macrophages and adipocytes

Chang, Hsiao Pei; Wang, M. L.; Hsu, Ching‐Yun; Liu, M. E.; Chan, M. H.; Chen, Yue‐Hwa

doi:10.1038/ijo.2011.12

Cited by 35 publications

(31 citation statements)

References 44 publications

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“…The increased accumulation of macrophages in the epididymal adipose tissue of mice fed high-fat diets was reduced with i.p. injections of I3C, and in vitro studies also showed that I3C mixed in co-cultures of macrophages and adipocytes, led to decreases in inflammatory factors, IL-6 and nitrite production (Chang et al, 2011). …”

Section: Discussionmentioning

confidence: 99%

Natural indoles, indole-3-carbinol and 3,3′-diindolymethane, inhibit T cell activation by staphylococcal enterotoxin B through epigenetic regulation involving HDAC expression

Busbee

Nagarkatti

2014

Toxicology and Applied Pharmacology

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Staphylococcal entertoxin B (SEB) is a potent exotoxin produced by the Staphylococcus aureus. This toxin is classified as a superantigen because of its ability to directly bind with MHC II class molecules followed by activation of a large proportion of T cells bearing specific Vβ-T cell receptors. Commonly associated with classic food poisoning, SEB has also been shown to induce toxic shock syndrome, and is also considered to be a potential biological warfare agent because it is easily aerosolized. In the present study, we assessed the ability of indole-3-carbinol (I3C) and one of its byproducts, 3,3′-diindolylmethane (DIM), found in cruciferous vegetables, to counteract the effects of SEB-induced activation of T cells in mice. Both I3C and DIM were found to decrease the activation, proliferation, and cytokine production by SEB-activated Vβ8+ T cells in vitro and in vivo. Interestingly, inhibitors of histone deacetylase class I (HDAC-I), but not class II (HDAC-II), showed significant decrease in SEB-induced T cell activation and cytokine production, thereby suggesting that epigenetic modulation plays a critical role in the regulation of SEB-induced inflammation. In addition, I3C and DIM caused a decrease in HDAC-I but not HDAC-II in SEB-activated T cells, thereby suggesting that I3C and DIM may inhibit SEB-mediated T cell activation by acting as HDAC-I inhibitors. These studies not only suggest for the first time that plant-derived indoles are potent suppressors of SEB-induced T cell activation and cytokine storm but also that they may mediate these effects by acting as HDAC inhibitors.

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Section: Discussionmentioning

confidence: 99%

Natural indoles, indole-3-carbinol and 3,3′-diindolymethane, inhibit T cell activation by staphylococcal enterotoxin B through epigenetic regulation involving HDAC expression

Busbee

Nagarkatti

2014

Toxicology and Applied Pharmacology

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“…Since BC and its primary metabolite DIM recently have been shown to produce anti-inflammatory and immunoregulatory effects in vitro (16)(17)(18)22), these compounds have the potential to elicit protective effects in diseases characterized by chronic inflammation. The current conventional medicines for Crohn's disease, a chronic inflammatory disease of the gastrointestinal tract, can be accompanied by severe adverse effects so many patients have turned towards natural and complementary therapies as part of their treatment regimens.…”

Section: Discussionmentioning

confidence: 99%

“…For histological analysis, a I cm section from the distal colon was fixed in 2% paraformaldehyde, processed in the Shandon Citadel 2000 Automated Tissue Processor (Thermo Fisher Scientific, Waltham, MA) with vacuum unit, embedded using the Shandon Histocentre 2 Embedding unit, sectioned at 7 urn using the Thermo Shandon Finesse 325 microtome, and stained with hematoxylin and eosin (H&E) in the Shandon Veristain 24-4 Slide Stainer. Colons were assessed microscopically by a blinded individual to determine the severity of inflammation based on an established scoring table (16). Briefly, colon damage was based on a combination of the severity of inflammatory cell infiltration into the tissue and the severity of tissue lesions.…”

Section: Colon Processing and Histologymentioning

confidence: 99%

“…It has been documented that BC can suppresses inflammation in vitro and in vivo in part by inhibiting NF-KB activation and decreasing production of inflammatory mediators (15)(16)(17)(18). Therefore, the potential exists for this compound to be effective in reducing the severity ofchronic inflammatory diseases including Crohn's disease and ulcerative colitis, which are inflammatory bowel diseases.…”

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confidence: 99%

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Indole-3-Carbinol Exerts Sex-Specific Effects in Murine Colitis

et al. 2012

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Due to the severe adverse effects that can accompany conventional therapies for Crohn's disease, the search for natural complementary therapies has increased dramatically in recent years. Indole-3-carbinol (I3C), a constituent of cruciferous vegetables, possesses anti-inflammatory properties; however, its effects on intestinal inflammation have yet to be evaluated. To test the hypothesis that I3C dampens intestinal inflammation, C57B1/6 mice were treated with I3C and exposed to 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce colitis. Several parameters of disease severity and inflammation were subsequently evaluated. I3C dampened the disease severity, as indicated by decreased body weight loss and decreased severity of clinical signs. Interestingly, this effect was observed in female but not male mice, which displayed a trend towards exacerbated colitis. Differential effects were observed in the profiles of cytokine production, as the production of pro-inflammatory cytokines was increased in males. The sex-specific effect of I3C in TNBS-induced colitis is a novel finding and warrants further investigation since this is a common dietary compound and is also available commercially.

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“…Interestingly, in this model I3C did not show protective effects. When male C57BL/6 mice received a HFD and were treated intraperitoneally with I3C for 12 weeks, this resulted in a profound improvement of metabolic inflammation in adipose tissue by the substantial decrease of macrophage infiltration and their cytokine production [21].…”

Section: Further Beneficial Examples For Indole Derivativesmentioning

confidence: 99%

Cruciferous vegetables: prototypic anti-inflammatory food components

Tilg

2015

Clin Phytosci

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There is increasing evidence that food components contribute to the pathogenesis of various disorders such as inflammatory bowel diseases, atherosclerosis, cancer or type 2 diabetes. Dietary factors especially enriched in Western diet cause and promote inflammatory processes throughout the organism involving various pathways but mainly the induction of pro-inflammatory cytokines. In contrast, there is increasing evidence that certain food components such as present in cruciferous vegetables have important anti-inflammatory properties. Cruciferous vegetables contain large amounts of various indole derivatives and are able via these components to activate aryl hydrocarbon receptors (AhR). Activation of these intracellular receptors results in potent intestinal immune modulation including regulation and maintenance of intestinal intraepithelial lymphocytes and innate lymphoid cells, induction of the key barrier cytokine interleukin-22 and manipulation of the intestinal microbiota. Lack of AhR is associated with an impaired barrier function and increased intestinal vulnerability suggesting that the continuous presence of dietary AhR ligands may be of importance throughout life. Sulforaphane, an isothiocyanate compound of cruciferous vegetables, also exerts mainly anti-inflammatory properties on immune processes. Therefore, evidence is accumulating that certain food components are healthy by targeting intestinal immune responses and reshaping the microbiota.

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Suppression of inflammation-associated factors by indole-3-carbinol in mice fed high-fat diets and in isolated, co-cultured macrophages and adipocytes

Cited by 35 publications

References 44 publications

Natural indoles, indole-3-carbinol and 3,3′-diindolymethane, inhibit T cell activation by staphylococcal enterotoxin B through epigenetic regulation involving HDAC expression

Natural indoles, indole-3-carbinol and 3,3′-diindolymethane, inhibit T cell activation by staphylococcal enterotoxin B through epigenetic regulation involving HDAC expression

Indole-3-Carbinol Exerts Sex-Specific Effects in Murine Colitis

Cruciferous vegetables: prototypic anti-inflammatory food components

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