IL-1 in Colon Inflammation, Colon Carcinogenesis and Invasiveness of Colon Cancer

Voronov, Elena; Apte, Ron N.

doi:10.1007/s12307-015-0177-7

Cited by 103 publications

(89 citation statements)

References 159 publications

(233 reference statements)

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“…Neutrophil infiltration during colitis-associated CRC is well appreciated to drive IL-1β release in the tumor microenvironment, another strong activator of NF-κB in IECs and tumor cells [51]. Nonetheless, IL-1β can also activate the Wnt-β-catenin signaling in CRC by AKT-dependent glycogen synthase kinase 3β (GSK3β) inactivation [52]. Remarkably, RIPK3-deficient mice exhibited a strong and uniform translocation of β-catenin to the cytoplasm and/or nucleus of IECs in the dysplastic areas of the colon.…”

Section: Discussionmentioning

confidence: 99%

Critical function of the necroptosis adaptor RIPK3 in protecting from intestinal tumorigenesis

et al. 2016

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Necroptosis is a programmed form of non-apoptotic cell death that requires the kinase activity of the receptor interacting protein kinase 3 (RIPK3). Although in vitro data suggests that cancer cells lacking expression of RIPK3 are invasive, the physiological role of RIPK3 in a disease-relevant setting remains unknown. Here we provide evidence that RIPK3 has a critical role in suppressing colorectal cancer (CRC). RIPK3-deficient mice were highly susceptible to colitis-associated CRC and exhibited greater production of pro-inflammatory mediators and tumor promoting factors. Tumorigenesis in RIPK3-deficiency resulted from uncontrolled activation of NF-κB, STAT3, AKT and Wnt-β-catenin signaling pathways that enhanced the ability of intestinal epithelial cells (IECs) to aberrantly proliferate in the face of the sustained inflammatory microenvironment and promote CRC. We found that RIPK3 expression is reduced in tumors from patients with inflammatory bowel diseases, and further confirmed that expression of RIPK3 is downregulated in human CRC and correlated with cancer progression. Thus, our results reveal that the necroptosis adaptor RIPK3 has key anti-inflammatory and anti-tumoral functions in the intestine, and define RIPK3 as a novel colon tumor suppressor.

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Section: Discussionmentioning

confidence: 99%

Critical function of the necroptosis adaptor RIPK3 in protecting from intestinal tumorigenesis

et al. 2016

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“…In this study, we found that miR-135a mimic alleviated DSS-induced inflammation by down-regulating IL-1β and TNF-ɑ expressions and productions in Caco-2 and HT-29 cells. IL-1β and TNF-ɑ are two major mediators of the inflammatory response and generations of IL-1β and TNF-ɑ precipitate acute attacks of systemic or local inflammation or chronic diseases [44][45][46]. Therefore, blocking proinflammatory cytokines (IL-1β and TNF-ɑ) by targeting miRNA may serve as a novel potential method to treat inflammatory diseases.…”

Section: Stat3 Inhibition Blocked the Anti-inflammatory Effect Of Mirmentioning

confidence: 99%

miR-135a Protects Dextran Sodium Sulfate-Induced Inflammation in Human Colorectal Cell Lines by Activating STAT3 Signal

Zhang

Liu

Shang

et al. 2018

Cell Physiol Biochem

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Background/Aims: miR-135a is reduced in several cancers and has been suggested to mediate immune and inflammatory responses. However, the effect of miR-135a on inflammatory bowel diseases was obscure. This study firstly attempted to investigate the hypothesis that miR-135a alleviates dextran sodium sulfate (DSS)-induced inflammation in colonic cells and potential mechanisms are also studied. Methods: Caco-2 and HT-29 cells in this study were treated with DSS, miR-135a mimic, and S3I-201, and then CKK-8 assay was used to test cell viability. Expressions of miR-135a, cytokines, and signal transducers and activators of transcription factors (STATs) were determined by RT-PCR. Also, cytokine productions were further tested by using ELISA kits. Activation or inactivation of STAT3 signal was validated by western blotting analysis. Results: The results showed that DSS markedly downregulated miR-135a expression (P< 0.05) and induced inflammatory response in Caco-2 and HT-29 cells evidenced by the up regulations and productions of interleukin-1β (IL-1β) and tumor necrosis factor-ɑ (TNF-ɑ) (P< 0.05). Transfection with miR-135a mimic significantly alleviated DSS-induced upregulation and productions of IL-1β and TNF-ɑ in Caco-2 and HT-29 cells (P< 0.05). STATs were analyzed and miR-135a mimic treatment reversed STAT3 downregulation in DSS-challenged Caco-2 and HT-29 cells compared with the mimic control (P< 0.05). Also, STAT3 phosphorylation was inhibited in DSS-challenged Caco-2 cells and miR-135a mimic activated STAT3 signal (P< 0.05). S3I-201, an inhibitor of STAT3 signal, further used to inactivate STAT3 signal and the results showed that S3I-201 blocked the anti-inflammatory effect of miR-135a mimic on Caco-2 and HT-29 cells evidenced by the lowered expressions and productions of proinflammatory cytokines ((IL-1β and TNF-ɑ) (P< 0.05). Conclusion: Our results indicated that miR-135a alleviated DSS-induced inflammation and activated STAT3 signal in colonic cells. Inhibition of STAT3 reversed the anti-inflammatory function of miR-135a by regulating proinflammatory cytokines. Thus, STAT3 signal might serve, at least in part, as the potential mechanism of miR-135a-mediated anti-inflammatory effect in colonic cells.

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“…12 The increase in the expression of representative inflammatory cytokines in IBD (such as IL-1β and TNF-α) may be the main cause of inflammatory cell activation. 13,14 On the other hand, COX-2 is an early immune gene expressed in inflammatory cells (such as macrophages) during the stimulation of inflammation and cytokine production, but is not expressed during normal conditions. 15 Thus, the genes that encode inflammatory factors in the digestive system, which damage and cause inflammation in the tissue after vigorous physical exercise, are similar to those in the acute phase response to inflammation by infection and those involved in IBD.…”

Section: E23mentioning

confidence: 99%

The Differential Impact Of High-Intensity Swimming Exercise and Inflammatory Bowel Disease On IL-1b, TNF-a, and COX-2 Gene Expression in the Small Intestine and Colon in Mice

Choi

2018

JOMH

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IL-1 in Colon Inflammation, Colon Carcinogenesis and Invasiveness of Colon Cancer

Cited by 103 publications

References 159 publications

Critical function of the necroptosis adaptor RIPK3 in protecting from intestinal tumorigenesis

Critical function of the necroptosis adaptor RIPK3 in protecting from intestinal tumorigenesis

miR-135a Protects Dextran Sodium Sulfate-Induced Inflammation in Human Colorectal Cell Lines by Activating STAT3 Signal

The Differential Impact Of High-Intensity Swimming Exercise and Inflammatory Bowel Disease On IL-1b, TNF-a, and COX-2 Gene Expression in the Small Intestine and Colon in Mice

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