Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
PZ HTL SA
GLOBETECH PUBLISHING LLC

Cytokine Identified That Causes Mucositis in Cancer Therapy Patients

By BiotechDaily International staff writers
Posted on 04 Mar 2014
The action of the cytokine interleukin 1-beta (IL-1beta) has been found to underlie the onset of mucositis, a common, severe side effect of chemotherapy and irradiation of cancer patients.

Mucositis occurs as a result of cell death in reaction to chemo- or radiotherapy. The mucosal lining of the mouth becomes thin, may slough off, and then become red, inflamed, and ulcerated. Ulcers may range from 0.5 centimeters to greater than four centimeters. Oral mucositis can be severely painful with the degree of pain usually related to the extent of the tissue damage. Due to pain, the patient may experience trouble speaking, eating, or even opening the mouth. Mucositis is often a major reason for premature suspension of anticancer therapy.

To study the molecular mechanisms responsible for mucositis investigators at the Hebrew University of Jerusalem (Israel) genetically engineered a line of mice to lack the gene that encodes the enzyme E3 beta-TrCP (beta-transducin repeat containing E3 ubiquitin protein ligase) in their gut epithelium. Deletion of beta-TrCP in the gut deregulated the cell cycle, induced a DNA damage response (DDR), and abolished the epithelium barrier function, resulting in a lethal mucosal inflammation that mimicked human mucositis.

Examination of these animals at the molecular level revealed that epithelial-derived IL-1beta, likely induced by DDR independently of NF-kappaB, was a major culprit, and initiated the pathology by compromising epithelial tight junctions. IL-1beta is a member of the interleukin 1 family of cytokines. This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1. This cytokine is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. The induction of cyclooxygenase-2 by this cytokine in the central nervous system was found to contribute to inflammatory pain hypersensitivity.

The investigators reported in the January 27, 2013, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) that antibody neutralization of IL-1beta prevented epithelial tight junction dysfunction and alleviated mucositis in beta-TrCP–deficient mice. They suggested that IL-1beta antagonists should be considered for prevention and treatment of mucositis.

Related Links:

Hebrew University of Jerusalem 




comments powered by Disqus

Channels

Genomics/Proteomics

view channel
Image: This novel, flexible film that can react to light is a promising step toward an artificial retina (Photo courtesy of the American Chemical Society).

Novel Nanofilm May Be Artificial Retina Precursor

Researchers have used advanced nanotechnology techniques to develop a light-sensitive film that has potential for future artificial retina applications. Investigators at the Hebrew University of Jerusalem... Read more

Drug Discovery

view channel
Image: Disruption and removal of malaria parasites by the experimental drug (+)-SJ733 (Photo courtesy of the University of California, San Francisco).

Experimental Antimalaria Drug Induces the Immune System to Destroy Infected Red Blood Cells

An experimental drug for the treatment of malaria was found to induce morphological changes in infected erythrocytes that enabled the immune system to recognize and eliminate them. Investigators at... Read more

Biochemistry

view channel

Blocking Enzyme Switch Turns Off Tumor Growth in T-Cell Acute Lymphoblastic Leukemia

Researchers recently reported that blocking the action of an enzyme “switch” needed to activate tumor growth is emerging as a practical strategy for treating T-cell acute lymphoblastic leukemia. An estimated 25% of the 500 US adolescents and young adults diagnosed yearly with this aggressive disease fail to respond to... Read more

Business

view channel

R&D Partnership Initiated to Reduce Development Time for New Drugs

nanoPET Pharma, GmbH (Berlin, Germany) signed an open-ended framework contract with the international pharmaceutical company Boehringer Ingelheim (Ridgefield, CT, USA). By developing customized contrast agents for research in both basic and preclinical studies, nanoPET Pharma will contribute to the enhancement of Boehringer... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.