Journal article
Nematode Asparaginyl-tRNA Synthetase Resolves Intestinal Inflammation in Mice with T-Cell Transfer Colitis
Clinical and vaccine immunology, Vol.20(2), pp.276-281
02/2013
DOI: 10.1128/CVI.00594-12
PMCID: PMC3571265
PMID: 23254300
Abstract
The therapeutic effects of a controlled parasitic nematode infection on the course of inflammatory bowel disease (IBD) have been demonstrated in both animal and human models. However, the inability of individual well-characterized nematode proteins to recreate these beneficial effects has limited the application of component immunotherapy to human disease. The nematodes that cause chronic human lymphatic filariasis,
Brugia malayi
and
Wuchereria bancrofti
, are among the parasites that induce immune suppression. Filarial lymphatic pathology has been shown to involve NF-κB pathway-dependent production of vascular endothelial growth factor (VEGF), and stimulation of VEGF expression has also been reported by interleukin 8 (IL-8) via NF-κB pathways. Previously, we have shown that the filarial asparaginyl-tRNA synthetase (rBmAsnRS) interacts with IL-8 receptors using a combination of extracellular loops that differ from those bound by IL-8. To test the hypothesis that rBmAsnRS might induce an anti-inflammatory effect
in vivo
, we studied the effects of rBmAsnRS in an established murine colitis model using T-cell transfer mice. T-cell transfer colitis mice treated intraperitoneally with 100 μg of rBmAsnRS four times over 2 weeks showed resolution of cellular infiltration in the colonic mucosa, along with induction of a CD8
+
cellular response. In addition, rBmAsnRS induced a rise in IL-10 production from CD3
+
and lipopolysaccharide (LPS)- and cytosine phosphate guanosine (CPG)-stimulated splenic cells. In summary, this work demonstrates a novel anti-inflammatory nematode protein, supports the hygiene hypothesis, and supports continued refinement of alternative immunotherapies for treatment of IBD.
Details
- Title: Subtitle
- Nematode Asparaginyl-tRNA Synthetase Resolves Intestinal Inflammation in Mice with T-Cell Transfer Colitis
- Creators
- Michael A Kron - Department of Medicine, Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USAAhmed Metwali - Division of Gastroenterology, Department of Internal Medicine, University of Iowa Carver College of Medicine and VAHC, Iowa City, IowaSanja Vodanovic-Jankovic - Department of Medicine, Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USADavid Elliott - Division of Gastroenterology, Department of Internal Medicine, University of Iowa Carver College of Medicine and VAHC, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Clinical and vaccine immunology, Vol.20(2), pp.276-281
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/CVI.00594-12
- PMID
- 23254300
- PMCID
- PMC3571265
- ISSN
- 1556-6811
- eISSN
- 1556-679X
- Language
- English
- Date published
- 02/2013
- Academic Unit
- Gastroenterology and Hepatology; Internal Medicine
- Record Identifier
- 9984094516802771
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