title: Increased expression of soluble form of vascular cell adhesion molecule-1 aggravates autoimmune arthritis in MRL-Fas(lpr) mice.
abstract: Vascular cell adhesion molecule-1 (VCAM-1, CD106) is important in leukocyte trafficking and its increased expression is associated with a number of chronic inflammatory diseases, including rheumatoid arthritis (RA). A soluble form of VCAM-1 (sVCAM-1) is generated by shedding of the membrane-bound molecule. The concentration of sVCAM-1 is increased in the sera of RA patients, but its pathological role has not been elucidated. The effect of sVCAM-1 relative to protection or aggravation of disease on the development of spontaneous arthritis was examined in an animal model of RA, namely MRL-Fas(lpr) mice (which display a disease resembling human RA), by generation of sVCAM-1 transgenic MRL-Fas(lpr) mice. Transgenic MRL-Fas(lpr) mice that expressed sVCAM-1 had higher incidence and increased severity of arthritis associated with higher levels of serum IgG rheumatoid factor compared with non-transgenic MRL-Fas(lpr) mice. These results suggest that sVCAM-1 plays an arthritogenic role in the development of inflammatory arthritis in MRL-Fas(lpr) mice and may present an important target for therapeutic strategy of RA.
authors.affiliation: Department of Anatomy and Embryology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, Biomolecular and Integrated Medical Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Oishi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Mizuki
authors.forename: Miho
authors.initials: M
authors.lastname: Terada
authors.forename: Megumi
authors.initials: M
authors.lastname: Kudo
authors.forename: Kimi
authors.initials: K
authors.lastname: Araki
authors.forename: Masatake
authors.initials: M
authors.lastname: Araki
authors.forename: Masato
authors.initials: M
authors.lastname: Nose
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D012217:Rheumatoid Factor / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D007074:Immunoglobulin G; D019010:Vascular Cell Adhesion Molecule-1; D012217:Rheumatoid Factor