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Increased expression of soluble form of vascular cell adhesion molecule‐1 aggravates autoimmune arthritis in MRL‐ Fas lpr mice
Author(s) -
Oishi Hisashi,
Mizuki Shinichi,
Terada Miho,
Kudo Megumi,
Araki Kimi,
Araki Masatake,
Nose Masato,
Takahashi Satoru
Publication year - 2007
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/j.1440-1827.2007.02165.x
Subject(s) - rheumatoid arthritis , arthritis , medicine , immunology , genetically modified mouse , autoimmune disease , transgene , cell adhesion molecule , antibody , chemistry , gene , biochemistry
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.