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Related Concept Videos

Inflammatory Bowel Disease I: Ulcerative Colitis01:27

Inflammatory Bowel Disease I: Ulcerative Colitis

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Introduction
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
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Inflammatory Bowel Disease II: Crohn's Disease01:30

Inflammatory Bowel Disease II: Crohn's Disease

709
Introduction
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
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Drugs for Treatment of Ulcerative Colitis in IBD01:29

Drugs for Treatment of Ulcerative Colitis in IBD

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Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide...
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Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy01:30

Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy

519
Various diagnostic tests are employed in the diagnostic process for Inflammatory Bowel Disease (IBD), particularly to differentiate between Crohn's disease and ulcerative colitis.
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the...
519
Renewal of Intestinal Stem Cells01:23

Renewal of Intestinal Stem Cells

2.9K
The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
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Related Experiment Video

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Induction of Intestinal Inflammation by Adoptive Transfer of CBir1 TCR Transgenic CD4+ T Cells to Immunodeficient Mice
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Colitis-induced IL11 promotes colon carcinogenesis.

Hong Wang1, David H Wang2, Xu Yang1

  • 1Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.

Carcinogenesis
|November 16, 2020
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Summary

Interleukin-11 (IL11) drives colon cancer development during colitis. Inhibiting IL11 signaling significantly reduced colitis-associated colon cancer in mice, revealing IL11 as a key factor in cancer promotion.

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Modeling Colitis-Associated Cancer with Azoxymethane AOM and Dextran Sulfate Sodium DSS
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Modeling Colitis-Associated Cancer with Azoxymethane AOM and Dextran Sulfate Sodium DSS
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Modeling Colitis-Associated Cancer with Azoxymethane AOM and Dextran Sulfate Sodium DSS

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Area of Science:

  • Gastroenterology
  • Oncology
  • Molecular Biology

Background:

  • Colitis is a known risk factor for colorectal cancer, but the underlying mechanisms are not fully understood.
  • Identifying factors that promote cancer during colitis is crucial for developing effective prevention and treatment strategies.

Purpose of the Study:

  • To investigate the role of Interleukin-11 (IL11) in colitis-associated colon cancer.
  • To elucidate the mechanism by which IL11 promotes colon carcinogenesis in the context of colitis.

Main Methods:

  • Gene expression profiling in dextran sulfate sodium (DSS)-induced colitis mouse models.
  • Analysis of STAT3 phosphorylation (pSTAT3) in colitis and tumors.
  • Utilizing IL11 receptor (IL11Rα1) knockout mice to assess IL11 signaling.
  • Employing a recombinant IL11 antagonist mutein to inhibit IL11 signaling during colitis.

Main Results:

  • IL11 was found to be upregulated in colitis tissues, colon tumors (induced by PhIP/DSS), and human colorectal cancer.
  • Colitis-induced IL11 activates STAT3 in colon crypt epithelial cells, evidenced by abolished pSTAT3 in IL11Rα1 knockout mice.
  • Colon carcinogenesis was significantly reduced in IL11Rα1 knockout mice.
  • Inhibition of IL11 signaling attenuated colitis-promoted carcinogenesis.

Conclusions:

  • Colitis-induced IL11 plays a critical role in promoting colon cancer.
  • IL11 facilitates the development of colon cancer from premalignant cells by creating a cancer-promoting microenvironment.
  • Targeting IL11 signaling presents a potential therapeutic strategy for preventing colitis-associated colorectal cancer.