title: Chitin microparticles for the control of intestinal inflammation.
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.
authors.affiliation: Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nagatani
authors.forename: Sen
authors.initials: S
authors.lastname: Wang
authors.forename: Victoria
authors.initials: V
authors.lastname: Llado
authors.forename: Cindy W
authors.initials: CW
authors.lastname: Lau
authors.forename: Zongxi
authors.initials: Z
authors.lastname: Li
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizoguchi
authors.forename: Cathryn R
authors.initials: CR
authors.lastname: Nagler
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Shibata
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Reinecker
authors.forename: J Rodrigo
authors.initials: JR
authors.lastname: Mora
authors.forename: Emiko
authors.initials: E
authors.lastname: Mizoguchi
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D055252:Cell-Derived Microparticles; D002686:Chitin / Q000627:therapeutic use*; D003092:Colitis / Q000209:etiology* / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D019673:Genes, T-Cell Receptor alpha / Q000502:physiology; D007249:Inflammation / Q000517:prevention & control*; D007371:Interferon-gamma / Q000378:metabolism; D007422:Intestines / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D002686:Chitin; D007371:Interferon-gamma; D016264:Dextran Sulfate