title: 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.
authors.affiliation: 1 Development Division, Ryusendo Co. Ltd. , Toshimaku, Tokyo, Japan .
authors.forename: Orie
authors.initials: O
authors.lastname: Yoshinari
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Shiojima
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Moriyama
authors.forename: Junichi
authors.initials: J
authors.lastname: Shinozaki
authors.forename: Takahisa
authors.initials: T
authors.lastname: Nakane
authors.forename: Kazuo
authors.initials: K
authors.lastname: Masuda
authors.forename: Manashi
authors.initials: M
authors.lastname: Bagchi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism*; D002645:Chickens; D024043:Collagen Type II / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007376:Interleukin-2 / Q000097:blood; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D012995:Solubility; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014867:Water
chemical_list: D015704:CD4 Antigens; D024043:Collagen Type II; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6; D053773:Transforming Growth Factor beta1; D014867:Water