Inflamed site-specific delivery of bone marrow-derived cells carrying IL-1Ra.
A gene delivery system using bone marrow-derived CD11b(+)CD18(+) cells and their interaction with adhesion molecules was established. After transplantation into mice, these vehicle cells may be recruited into glomeruli upon lipopolysaccharide (LPS) treatment, and the number of recruited cells corresponds to the expression of intercellular adhesion molecule-1 (ICAM-1) in glomeruli. Using this system, interleukin-1 receptor antagonist (IL-1Ra) was delivered into animal models of glomerulonephritis evoked by anti-glomerular basement membrane antibody (anti-GBM nephritis). Urinary albumin excretion and the serum creatinine level were significantly elevated after anti-GBM antibody injection in mock-treated mice, whereas they were suppressed in the IL-1Ra-treated mice. Histological analysis revealed that glomerular injuries were also suppressed in IL-1Ra-treated mice. We further confirmed that specificity for inflamed glomeruli was significantly enhanced by a combination of the Cre/loxP system with the IL-1beta promoter. These data suggested that our novel system may be used as a therapeutic intervention for glomerulonephritis.
Yokoo
Takashi
T
Division of Nephrology and Hypertension, Department of Internal Medicine, Institute of DNA Medicine, Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, 105-8461 Japan.
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000628:therapy*; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D015316:Genetic Therapy / Q000379:methods*; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins / Q000235:genetics*
D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins