Chitin microparticles for the control of intestinal inflammation

Katsuya Nagatani, Sen Wang, Victoria Llado, Cindy W. Lau, Zongxi Li, Atsushi Mizoguchi, Cathryn R. Nagler, Yoshimi Shibata, Hans Christian Reinecker, J. Rodrigo Mora, Emiko Mizoguchi

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1698-1710
Number of pages13
JournalInflammatory bowel diseases
Volume18
Issue number9
DOIs
StatePublished - Sep 2012
Externally publishedYes

Keywords

  • animal model
  • chitin
  • chitinase
  • colitis
  • cytokine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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