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Pattern Recognition Scavenger Receptors, SR-A and CD36, Have an Additive Role in the Development of Colitis in Mice

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Abstract

The multifunctional pattern recognition scavenger receptors, SR-A and CD36, are predominantly expressed by lamina propria macrophages and considered important in innate immunity. We examined the role of these receptors in the pathophysiology of inflammatory bowel disease. Colitis was induced in wild type (WT), SR-A−/−, CD36−/−, and SR-A/CD36 double deficient mice by administering DSS. DSS-induced moderately severe colitis in WT mice was manifested by weight loss, reduced hematocrit, and pathology. SR-A/CD36 double deficient mice developed significantly more severe colitis as indicated by anemia (P < 0.01), decreased colonic length due to inflammation (P < 0.01), and lesions when compared with WT and single deficient animals. Serum amyloid A was significantly more elevated in SR-A/CD36−/− mice (P < 0.01) compared with WT and single deficient animals. However, the spleens of WT mice (P < 0.05) were significantly enlarged. Inflammatory cytokine levels were considerably increased in WT mice (IL-6 P < 0.001, TNFα P < 0.01). In contrast, SR-A deficient mice maintained more normal body and splenic weight and developed less severe colonic lesions compared to other groups. In conclusion, our data indicate that SR-A/CD36 double deficiency leads to more severe colonic lesions and dysregulated inflammatory response as compared with single SR-A or CD36 deficiency in colitis, suggesting additive effects between these two receptors in this model.

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Abbreviations

DSS:

Dextran sodium sulphate

INF-γ:

Interferon gamma

IL-6:

Interleukin-6

LDL:

Low-density lipoprotein

LPS:

Lipopolysaccharide

LTA:

Lipoteichoic acid

MФ:

Macrophage

SR-A:

Scavenger receptor A

TNFα:

Tumor necrosis factor

WT:

Wildtype

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Acknowledgment

This study was partially supported by the National Institutes of Health grant NCCAM-AT1490 and NCRR P20RR020145,COHR-Pilot Project (H. S. Oz).

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Authors and Affiliations

  1. Center for Oral Health Research, College of Dentistry, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY, 40536, USA

    Helieh S. Oz

  2. Department of Internal Medicine, University of Kentucky Medical Center, Lexington, KY, USA

    Helieh S. Oz, Jian Zhong & Willem J. S. de Villiers

  3. Division of Digestive Diseases, University of Kentucky Medical Center, Lexington, KY, USA

    Jian Zhong & Willem J. S. de Villiers

Authors
  1. Helieh S. Oz
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  2. Jian Zhong
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  3. Willem J. S. de Villiers
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Correspondence to Helieh S. Oz.

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H. S. Oz and J. Zhong contributed equally to this work.

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Oz, H.S., Zhong, J. & de Villiers, W.J.S. Pattern Recognition Scavenger Receptors, SR-A and CD36, Have an Additive Role in the Development of Colitis in Mice. Dig Dis Sci 54, 2561–2567 (2009). https://doi.org/10.1007/s10620-008-0673-4

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  • DOI: https://doi.org/10.1007/s10620-008-0673-4

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