Researchers uncover key role for microRNA in inflammatory bowel disease

May 09, 2017

An international team of researchers has discovered that a microRNA produced by certain white blood cells can prevent excessive inflammation in the intestine. The study, "Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome," which will be published May 9 in The Journal of Experimental Medicine, shows that synthetic versions of this microRNA can reduce intestinal inflammation in mice and suggests a new therapeutic approach to treating patients with Crohn's disease or ulcerative colitis.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, affects almost 2 million people in the US. Although IBD is caused by a complex mix of genetic and environmental factors, it is thought to be initiated by an excessive immune response against bacteria in the gut. This immune response involves the recruitment of various white blood cells, such as neutrophils and monocytes, into the intestine and the activation of a protein complex in these cells known as the inflammasome. The inflammasome, in turn, activates the proinflammatory signaling molecules IL-1β and IL-18, which stimulate the further influx of white blood cells.

MicroRNAs are small RNA molecules that can bind and repress protein-coding messenger RNAs. An international team of researchers led by Eóin McNamee at the University of Colorado-Anschutz Medical Campus found that IBD patients showed increased levels of a microRNA called miR-223 during active bouts of inflammation. This microRNA was also elevated in laboratory mice with colitis.

miR-223 is produced by neutrophils and monocytes and has previously been shown to repress the messenger RNA encoding NLRP3, a key component of the inflammasome. McNamee and colleagues found that mice lacking miR-223 expressed higher levels of NLRP3, causing increased IL-1β production and enhanced susceptibility to intestinal inflammation.

In contrast, mice treated with lipid nanoparticles containing synthetic RNA molecules that mimic miR-223 showed lower levels of NLRP3 and IL-1β and were accordingly protected from experimentally induced colitis.

"Our study highlights the miR-223-NLRP3-IL-1β regulatory circuit as a critical component of intestinal inflammation," McNamee says. "miR-223 serves to constrain the level of NLRP3 inflammasome activation and provides an early brake that limits excessive inflammation. Genetic or pharmacologic stabilization of miR-223 may hold promise as a future novel therapy for active flares in IBD."
-end-
Neudecker et al., 2017. J. Exp. Med.http://bit.ly/miRNA-ColitisJEM

About The Journal of Experimental MedicineThe Journal of Experimental Medicine (JEM) features peer-reviewed research on immunology, cancer biology, stem cell biology, microbial pathogenesis, vascular biology, and neurobiology. All editorial decisions are made by research-active scientists in conjunction with in-house scientific editors. JEM provides free online access to many article types from the date of publication and to all archival content. Established in 1896, JEM is published by The Rockefeller University Press. For more information, visit jem.org.

Visit our Newsroom, and sign up for a weekly preview of articles to be published. Embargoed media alerts are for journalists only.

Follow JEM on Twitter at @JExpMed and @RockUPress.

Rockefeller University Press

Related Microrna Articles from Brightsurf:

Researchers identify microRNA that shows promise for hair regrowth
Researchers from North Carolina State University have identified a microRNA (miRNA) that could promote hair regeneration.

Atherosclerosis -- How a microRNA protects vascular integrity
Ludwig-Maximilian-Universitaet (LMU) in Munich researchers have discovered a hitherto unknown molecular function of a specific microRNA that preserves integrity of the endothelium and reduces the risk of atherosclerosis.

MicroRNA exhibit unexpected function in driving cancer
New research shows that both strands of microRNA cooperate to drive growth and aggressiveness across cancer types, suggesting that these molecules may be more central in deadly cancers than previously thought.

Investigators narrow in on a microRNA for treating multiple sclerosis
Investigators from Brigham and Women's Hospital have discovered a microRNA -- a small RNA molecule -- that increases during peak disease in a mouse model of MS and in untreated MS patients.

MicroRNA comprehensively analyzed
Messenger RNA transmits genetic information to the proteins, and microRNA plays a key role in the regulation of gene expression.

Novel strategy using microRNA biomarkers can distinguish melanomas from nevi
Melanoma is the least common but one of the most deadly skin cancers.

Methylation of microRNA may be a new powerful biomarker for cancer
Researchers from Osaka University found that levels of methylated microRNA were significantly higher in tissue and serum from cancer patients compared with that from normal controls.

New insight into microRNA function can give gene therapy a boost
Scientists at the University of Eastern Finland and the University of Oxford have shown that small RNA molecules occurring naturally in cells, i.e. microRNAs, are also abundant in cell nuclei.

Researchers unlock mysteries of complex microRNA oncogenes
A new collaborative study, led by researchers at McGill University's Goodman Cancer Research Centre (GCRC), and published in the journal Molecular Cell, uncovers novel functions for polycistronic microRNAs and showing how cancers such as lymphoma twist these functions to reorganize the information networks that control gene expression.

MicroRNA-like RNAs contribute to the lifestyle transition of Arthrobotrys oligospora
Lifestyle transition is a fundamental mechanism that fungi have evolved to survive and proliferate in different environments.

Read More: Microrna News and Microrna Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.