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Water-soluble undenatured type II collagen ameliorates collagen-induced arthritis in mice.

Abstract
Earlier studies have reported the efficacy of type II collagen (C II) in treating rheumatoid arthritis (RA). However, a few studies have investigated the ability of the antigenic collagen to induce oral tolerance, which is defined as active nonresponse to an orally administered antigen. We hypothesized that water-soluble undenatured C II had a similar effect as C II in RA. The present study was designed to examine the oral administration of a novel, water-soluble, undenatured C II (commercially known as NEXT-II) on collagen-induced arthritis (CIA) in mice. In addition, the underlying mechanism of NEXT-II was also identified. After a booster dose (collagen-Freund's complete adjuvant), mice were assigned to control CIA group, or NEXT-II treatment group, to which saline and NEXT-II were administered, respectively. The arthritis index in the NEXT-II group was significantly lower compared with the CIA group. Serum IL-6 levels in the NEXT-II group were significantly lower compared with the CIA group, while serum IL-2 level was higher. Furthermore, oral administration of NEXT-II enhanced the proportion of CD4+CD25+T (Treg) cells, and gene expressions of stimulated dendritic cells induced markers for regulatory T cells such as forkhead box p3 (Foxp3), transforming growth factor (TGF)-β1, and CD25. These results demonstrated that orally administered water-soluble undenatured C II (NEXT-II) is highly efficacious in the suppression of CIA by inducing CD4+CD25+ Treg cells.
AuthorsOrie Yoshinari, Yoshiaki Shiojima, Hiroyoshi Moriyama, Junichi Shinozaki, Takahisa Nakane, Kazuo Masuda, Manashi Bagchi
JournalJournal of medicinal food (J Med Food) Vol. 16 Issue 11 Pg. 1039-45 (Nov 2013) ISSN: 1557-7600 [Electronic] United States
PMID24175655 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • CD4 Antigens
  • Collagen Type II
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-6
  • Transforming Growth Factor beta1
  • Water
Topics
  • Administration, Oral
  • Animals
  • Arthritis, Experimental (blood, drug therapy, immunology, metabolism)
  • Arthritis, Rheumatoid (blood, drug therapy, immunology, metabolism)
  • CD4 Antigens (metabolism)
  • Chickens
  • Collagen Type II (administration & dosage, immunology, pharmacology, therapeutic use)
  • Dendritic Cells (metabolism)
  • Forkhead Transcription Factors (metabolism)
  • Gene Expression (drug effects)
  • Interleukin-2 (blood)
  • Interleukin-2 Receptor alpha Subunit (metabolism)
  • Interleukin-6 (blood)
  • Male
  • Mice
  • Mice, Inbred DBA
  • Solubility
  • T-Lymphocytes, Regulatory (metabolism)
  • Transforming Growth Factor beta1 (metabolism)
  • Water

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