Indole-3-carbinol inhibits LPS-induced inflammatory response by blocking TRIF-dependent signaling pathway in macrophages

Jiang, Jun; Kang, Tae-Bong; Shim, Do-Wan; Oh, Na Hyun; Kim, Tack Joong; Lee, Kwang Ho

doi:10.1016/j.fct.2013.03.040

Cited by 53 publications

(22 citation statements)

References 35 publications

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“…For example, recently DIM was shown to suppress lipopolysaccharide (LPS)-induced brain inflammation in the hippocampus of mice [ 34 ]. I3C was found to reduce cellular infiltration into the broncho-alveolar lavage fluid (BALF) of LPS-induced acute lung injury, while also decreasing proinflammatory cytokines, such as IL-6 and TNF-α, in the lungs [ 35 ]. Our laboratory has recently shown that I3C and DIM can suppress T cell activation by SEB through epigenetic regulation involving HDAC expression [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Natural Indoles, Indole-3-Carbinol (I3C) and 3,3’-Diindolylmethane (DIM), Attenuate Staphylococcal Enterotoxin B-Mediated Liver Injury by Downregulating miR-31 Expression and Promoting Caspase-2-Mediated Apoptosis

Busbee

Nagarkatti

2015

PLoS ONE

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Staphylococcal enterotoxin B (SEB) is a potent superantigen capable of inducing inflammation characterized by robust immune cell activation and proinflammatory cytokine release. Exposure to SEB can result in food poisoning as well as fatal conditions such as toxic shock syndrome. In the current study, we investigated the effect of natural indoles including indole-3-carbinol (I3C) and 3,3’-diindolylmethane (DIM) on SEB-mediated liver injury. Injection of SEB into D-galactosamine-sensitized female C57BL/6 mice resulted in liver injury as indicated by an increase in enzyme aspartate transaminase (AST) levels, induction of inflammatory cytokines, and massive infiltration of immune cells into the liver. Administration of I3C and DIM (40mg/kg), by intraperitonal injection, attenuated SEB-induced acute liver injury, as evidenced by decrease in AST levels, inflammatory cytokines and cellular infiltration in the liver. I3C and DIM triggered apoptosis in SEB-activated T cells primarily through activation of the intrinsic mitochondrial pathway. In addition, inhibitor studies involving caspases revealed that I3C and DIM-mediated apoptosis in these activated cells was dependent on caspase-2 but independent of caspase-8, 9 and 3. In addition, I3C and DIM caused a decrease in Bcl-2 expression. Both compounds also down-regulated miR-31, which directly targets caspase-2 and influences apoptosis in SEB-activated cells. Our data demonstrate for the first time that indoles can effectively suppress acute hepatic inflammation caused by SEB and that this may be mediated by decreased expression of miR-31 and consequent caspase-2-dependent apoptosis in T cells.

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Section: Discussionmentioning

confidence: 99%

Natural Indoles, Indole-3-Carbinol (I3C) and 3,3’-Diindolylmethane (DIM), Attenuate Staphylococcal Enterotoxin B-Mediated Liver Injury by Downregulating miR-31 Expression and Promoting Caspase-2-Mediated Apoptosis

Busbee

Nagarkatti

2015

PLoS ONE

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“…Treatment with I3C (25–100 μM) diminished the production of pro-inflammatory intermediaries like nitric oxide (NO), interleukin (IL)-6, and IL-1β in lipopolysaccharides (LPS)-induced Raw264.7 cells and THP-1 cells through suppression of the TRIF-dependent signaling pathway. Thus, it was shown that I3C had protective role in the treatment of inflammatory diseases including acute lung injury caused by microbial infection [41]. Treatment of lung cancer cells with I3C (400 μM) caused reduction in proliferation of cells, increased formations of fragmented DNA and apoptotic bodies, and induction of cell-cycle arrest at G0/G1 phase.…”

Section: Indole-3-carbinol and Lung Cancermentioning

confidence: 99%

Dietary agents for prevention and treatment of lung cancer

Khan¹,

Mukhtar²

2015

Cancer Letters

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Lung cancer is a prominent cause of cancer-associated mortality worldwide. The main reason for high mortality due to lung cancer is attributable to the fact that the diagnosis is generally made when it has spread beyond a curable stage and cannot be treated surgically or with radiation therapy. Therefore, new approaches like dietary modifications could be extremely useful in reducing lung cancer incidences. Several fruits and vegetables offer a variety of bioactive compounds to afford protection against several diseases, including lung cancer. A number of research studies involving dietary agents provide strong evidence for their role in the prevention and treatment of lung cancer, and have identified their molecular mechanisms of action and potential targets. In this review article, we summarize data from in-vitro and in-vivo studies and where available, in clinical trials, on the effects of some of the most promising dietary agents against lung cancer.

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“…It was shown that indole-3-carbinol has the ability to increase the activity of some anti-oxidant enzymes such as hemoxygenase-1 and glutathione transferase 16 . Besides, several studies had confirmed the anti-inflammatory activities of indole-3-carbinol in a variety of animal models such as aspirin-induced gastric ulcer 17 , liver fibrosis 18 , lipopolysaccharide-induced acute lung injury 19 and high fat diet-induced obesity 20 . In fact, indole-3-carbinol had been found to reduce the expression of pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α and NF-kB 18 19 21 .…”

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confidence: 96%

Indole-3-carbinol protects against cisplatin-induced acute nephrotoxicity: role of calcitonin gene-related peptide and insulin-like growth factor-1

El-Naga

Mahran

2016

Sci Rep

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Nephrotoxicity associated with the clinical use of the anticancer drug cisplatin is a limiting problem. Thus, searching for new protective measures is required. Indole-3-carbinol is a powerful anti-oxidant, anti-inflammatory and anti-tumor agent. The present study aimed to investigate the potential protective effect of indole-3-carbinol against cisplatin-induced acute nephrotoxicity in rats. Rats were pre-treated with 20 mg/kg indole-3-carbinol orally before giving cisplatin (7 mg/kg). Cisplatin-induced acute nephrotoxicity was demonstrated where relative kidney weight, BUN and serum creatinine were significantly increased. Increased oxidative stress was evident in cisplatin group where GSH and SOD tissue levels were significantly depleted. Also, lipid peroxidation and NOX-1 were increased as compared to the control. Additionally, renal expression of pro-inflammatory mediators was induced by cisplatin. Cisplatin-induced cell death was shown by increased caspase-3 and decreased expression of EGF, IGF-1 and IGF-1 receptor. Nephrotoxicity, oxidative stress, inflammation and apoptotic effects induced by cisplatin were significantly ameliorated by indole-3-carbinol pre-treatment. Besides, the role of CGRP in cisplatin-induced nephrotoxicity was explored. Furthermore, cisplatin cytotoxic activity was significantly enhanced by indole-3-carbinol pre-treatment in vitro. In conclusion, indole-3-carbinol provides protection against cisplatin-induced nephrotoxicity. Also, reduced expression of CGRP may play a role in the pathogenesis of cisplatin-induced renal injury.

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Indole-3-carbinol inhibits LPS-induced inflammatory response by blocking TRIF-dependent signaling pathway in macrophages

Cited by 53 publications

References 35 publications

Natural Indoles, Indole-3-Carbinol (I3C) and 3,3’-Diindolylmethane (DIM), Attenuate Staphylococcal Enterotoxin B-Mediated Liver Injury by Downregulating miR-31 Expression and Promoting Caspase-2-Mediated Apoptosis

Natural Indoles, Indole-3-Carbinol (I3C) and 3,3’-Diindolylmethane (DIM), Attenuate Staphylococcal Enterotoxin B-Mediated Liver Injury by Downregulating miR-31 Expression and Promoting Caspase-2-Mediated Apoptosis

Dietary agents for prevention and treatment of lung cancer

Indole-3-carbinol protects against cisplatin-induced acute nephrotoxicity: role of calcitonin gene-related peptide and insulin-like growth factor-1

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