Inflammatory Bowel Diseases

Skip Navigation LinksHome > May 2013 - Volume 19 - Issue 6 > RNase-L Deficiency Exacerbates Experimental Colitis and Coli...
Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0b013e318281f2fd
Original Basic Science Article

RNase-L Deficiency Exacerbates Experimental Colitis and Colitis-associated Cancer

Long, Tiha M. BS*; Chakrabarti, Arindam PhD; Ezelle, Heather J. PhD; Brennan-Laun, Sarah E. PhD; Raufman, Jean-Pierre MD; Polyakova, Irina MS; Silverman, Robert H. PhD; Hassel, Bret A. PhD*,‡,§,¶

Supplemental Author Material
Collapse Box


Background: The endoribonuclease RNase-L is a type-I interferon (IFN)-regulated component of the innate immune response that functions in antiviral, antibacterial, and antiproliferative activities. RNase-L produces RNA agonists of RIG-I–like receptors, sensors of cytosolic pathogen-associated RNAs that induce cytokines including IFN-β. IFN-β and RIG-I–like receptors signaling mediate protective responses against experimental colitis and colitis-associated cancer and contribute to gastrointestinal homeostasis. Therefore, we investigated a role for RNase-L in murine colitis and colitis-associated cancer and its association with RIG-I–like receptors signaling in response to bacterial RNA.

Methods: Colitis was induced in wild type–deficient and RNase-L–deficient mice (RNase-L−/−) by administration of dextran sulfate sodium (DSS). Colitis-associated cancer was induced by DSS and azoxymethane (AOM). Histological analysis and immunohistochemistry were performed on colon tissue to analyze immune cell infiltration and tissue damage after induction of colitis. Expression of cytokines was measured by quantitative real-time–PCR and ELISA.

Results: DSS-treated RNase-L−/− mice exhibited a significantly higher clinical score, delayed leukocyte infiltration, reduced expression of IFN-β, tumor necrosis factor α, interleukin-1β, and interleukin-18 at early times post-DSS exposure, and increased mortality as compared with wild-type mice. DSS/AOM-treated RNase-L−/− mice displayed an increased tumor burden. Bacterial RNA triggered IFN-β production in an RNase-L–dependent manner and provided a potential mechanism by which RNase-L contributes to the gastrointestinal immune response to microbiota and protects against experimental colitis and colitis-associated cancer.

Conclusions: RNase-L promotes the innate immune response to intestinal damage and ameliorates murine colitis and colitis-associated cancer. The RNase-L–dependent production of IFN-β stimulated by bacterial RNA may be a mechanism to protect against gastrointestinal inflammatory disease.

© Crohn's & Colitis Foundation of America, Inc.

You currently do not have access to this article.

You may need to:

Note: If your society membership provides for full-access to this article, you may need to login on your society’s web site first.


Article Tools


Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.