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Updated: Jul 16, 2026
Investigating Intestinal Inflammation in DSS-induced Model of IBD
Published on: February 1, 2012
Activation of toll-like receptor 3 protects against DSS-induced acute colitis
Matam Vijay-Kumar1, Huixia Wu, Jesse Aitken
1Department of Pathology and Laboratory Medicine, Epithelial Pathobiology Unit, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Background:
Mimetics of bacterial DNA, given orally or subcutaneously, protect mice from experimental colitis via a toll-like receptor (TLR)-9-dependent mechanism. The goal of the study was to define whether synthetic viral RNA, polyinosinic acid:cytidylic acid [poly(I:C)], which is also a potent immunomodulator, might also affect murine colitis and, if so, define whether such effects were mediated by TLR3, which is one of at least 4 known receptors for this viral RNA analog.
Methods:
Mice (C57BL6, IL-10KO, or TLR3 KO) were administered 1.5% dextran sodium sulfate (DSS) in drinking water for 7 days. Two hours before treatment with DSS, mice were given phosphate-buffered saline (PBS) or poly(I:C) 20 mug subcutaneously (s.c.), or 100 mug intragastrically (i.g.).
Results:
In wildtype mice s.c. administration of poly(I:C) dramatically protected against DSS-induced colitis as assessed by every parameter analyzed, which included body weight, rectal bleeding, colonic myeloperoxidase, histopathology, serum keratinocyte-derived chemokine, serum amyloid A, and lipocalin-2. In contrast, i.g. administration of poly(I:C) offered no protection in this colitis model nor did its administration activate the innate immune system as assessed by serologic parameters. Subcutaneous poly(I:C) protected against DSS-induced colitis equally well in C57BL6 and IL-10KO mice, indicating that this antiinflammatory cytokine is not required for such protection. Protection against colitis given by poly(I:C) treatment was ablated in TLR3 KO, indicating that the protective action of this viral RNA analog was mediated by this receptor.
Conclusions:
Activation of TLR3 on cells that are accessible by systemic, but not oral, administration of synthetic viral RNA results in protection against the acute inflammation that can ensue upon damage of the gut epithelium. Thus, this viral RNA analog, which is under clinical trials for other inflammatory disorders (e.g., lupus), may also have therapeutic value for inflammatory bowel disease.
Insights
Synthetic viral RNA (poly(I:C)) administered subcutaneously protects against experimental colitis in mice by activating toll-like receptor 3 (TLR3). Oral administration did not provide protection, highlighting the importance of systemic delivery for therapeutic effects in inflammatory bowel disease.
Area of Science:
- Immunology
- Gastroenterology
- Pharmacology
Background:
- Toll-like receptor (TLR) agonists, such as bacterial DNA mimetics, demonstrate protective effects against experimental colitis.
- Synthetic viral RNA analogs, like polyinosinic acid:cytidylic acid [poly(I:C)], are potent immunomodulators with potential therapeutic applications.
Purpose of the Study:
- To investigate the efficacy of poly(I:C) in a murine model of colitis.
- To determine if the protective effects of poly(I:C) against colitis are mediated by toll-like receptor 3 (TLR3).
Main Methods:
- Mice were induced with dextran sodium sulfate (DSS)-induced colitis.
- Poly(I:C) was administered either subcutaneously (s.c.) or intragastrically (i.g.) prior to DSS treatment.
- Experiments were conducted in wildtype, IL-10 knockout (KO), and TLR3 knockout (KO) mice.
Main Results:
- Subcutaneous administration of poly(I:C) significantly protected against DSS-induced colitis across multiple disease parameters.
- Intragastric administration of poly(I:C) did not confer protection and failed to activate the innate immune system.
- Protection mediated by subcutaneous poly(I:C) was independent of IL-10 but was abolished in TLR3 knockout mice, confirming TLR3 as the key mediator.
Conclusions:
- Systemic administration of synthetic viral RNA activates TLR3, leading to protection against acute gut epithelial inflammation.
- Poly(I:C) demonstrates therapeutic potential for inflammatory bowel disease, warranting further investigation in clinical trials.
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