Increased expression of soluble form of vascular cell adhesion molecule-1 aggravates autoimmune arthritis in MRL-Fas(lpr) mice.
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.
Oishi
Hisashi
H
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.
Mizuki
Shinichi
S
Terada
Miho
M
Kudo
Megumi
M
Araki
Kimi
K
Araki
Masatake
M
Nose
Masato
M
Takahashi
Satoru
S
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
D007074:Immunoglobulin G; D019010:Vascular Cell Adhesion Molecule-1; D012217:Rheumatoid Factor