Original Article

Chitin microparticles for the control of intestinal inflammation

  1. Katsuya Nagatani MD, PhD1,
  2. Sen Wang PhD1,
  3. Victoria Llado PhD1,
  4. Cindy W. Lau BS1,2,
  5. Zongxi Li MBBS1,3,
  6. Atsushi Mizoguchi MD, PhD2,4,
  7. Cathryn R. Nagler PhD5,
  8. Yoshimi Shibata PhD6,
  9. Hans-Christian Reinecker MD1,4,
  10. J. Rodrigo Mora MD, PhD1,4,
  11. Emiko Mizoguchi MD, PhD1,4,*

Article first published online: 12 JAN 2012

DOI: 10.1002/ibd.22874

Issue

Inflammatory Bowel Diseases

Inflammatory Bowel Diseases

Volume 18, Issue 9, pages 1698–1710, September 2012

Additional Information

How to Cite

Nagatani, K., Wang, S., Llado, V., Lau, C. W., Li, Z., Mizoguchi, A., Nagler, C. R., Shibata, Y., Reinecker, H.-C., Mora, J. R. and Mizoguchi, E. (2012), Chitin microparticles for the control of intestinal inflammation. Inflamm Bowel Dis, 18: 1698–1710. doi: 10.1002/ibd.22874

Author Information

  1. 1

    Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

  2. 2

    Molecular Pathology Unit, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

  3. 3

    Department of Immunology, China Medical University, Shenyang, Liaoning, China

  4. 4

    Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, Massachusetts

  5. 5

    Department of Pathology, Committee on Immunology, University of Chicago, Chicago, Illinois

  6. 6

    Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida

*Massachusetts General Hospital, GRJ 702, 55 Fruit St., Boston, MA 02114

Publication History

  1. Issue published online: 9 AUG 2012
  2. Article first published online: 12 JAN 2012
  3. Manuscript Accepted: 12 DEC 2011
  4. Manuscript Received: 19 NOV 2011

Funded by

  • National Institutes of Health. Grant Numbers: DK 80070, DK74454, DK64289, DK43351
  • Eli and Edythe L. Broad Medical Foundation
  • American Gastroenterological Association Foundation

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Keywords:

  • chitin;
  • chitinase;
  • colitis;
  • cytokine;
  • animal model

Abstract

Background:

Chitin is a polymer of N-acetylglucosamine with the ability to regulate innate and adaptive immune responses. However, the detailed mechanisms of chitin-mediated regulation of intestinal inflammation are only partially known.

Methods:

In this study chitin microparticles (CMPs) or phosphate-buffered saline (PBS) were orally administered to acute and chronic colitis models every 3 days for 6 consecutive weeks beginning at weaning age. The effects of this treatment were evaluated by histology, cytokine production, coculture study, and enteric bacterial analysis in dextran sodium sulfate (DSS)-induced colitis or T-cell receptor alpha (TCRα) knockout chronic colitis models.

Results:

Histologically, chitin-treated mice showed significantly suppressed colitis as compared with PBS-treated mice in both animal models. The production of interferon-gamma (IFN-γ) was upregulated in the mucosa of chitin-treated mice compared with control mice. The major source of IFN-γ-producing cells was CD4+ T cells. In mouse dendritic cells (DCs) we found that CMPs were efficiently internalized and processed within 48 hours. Mesenteric lymph nodes (MLNs) CD4+ T cells isolated from chitin-treated mice produced a 7-fold higher amount of IFN-γ in the culture supernatant after being cocultured with DCs and chitin as compared with the control. Proliferation of carboxyfluorescein succinimidyl ester (CFSE)low CD4+ T cells in MLNs and enteric bacterial translocation rates were significantly reduced in chitin-treated mice when compared with the control. In addition, CMPs improved the imbalance of enteric bacterial compositions and significantly increased interleukin (IL)-10-producing cells in noninflamed colon, indicating the immunoregulatory effects of CMPs in intestinal mucosa.

Conclusions:

CMPs significantly suppress the development of inflammation by modulating cytokine balance and microbial environment in colon. (Inflamm Bowel Dis 2012;)

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