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KMID : 1161420130160111039
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Journal of Medicinal Food
2013 Volume.16 No. 11 p.1039 ~ p.1045
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Water-Soluble Undenatured Type II Collagen Ameliorates Collagen-Induced Arthritis in Mice
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Yoshinari Orie
Shiojima Yoshiaki
Moriyama Hiroyoshi
Shinozaki Junichi
Nakane Takahisa
Masuda Kazuo
Bagchi Manashi
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Abstract
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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.
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KEYWORD
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CD4+CD25+Treg, collagen-induced arthritis, Foxp3, oral tolerance, rheumatoid arthritis, TGF-β, undenatured type II collagen
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