Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-1-3
pubmed:abstractText
In this study, we used genetically modified bone marrow-derived CD11b(+)CD18(+) vehicle cells to deliver IL-1 receptor antagonist (IL-1ra) for treatment of inflamed renal interstitium in an animal model of unilateral ureteral obstruction (UUO). Vehicle cells that expressed the ICAM-1 ligands, CD11b and CD18, were obtained from bone marrow cells of DBA/2j mice and adenovirally transduced with the IL-1ra gene or glucocerebrosidase (GC) gene ex vivo. In kidneys treated to develop UUO, levels of ICAM-1, IL-1 beta, and IL-1R expression increased within 3 days compared with contralateral untreated kidneys in the same mice. Similarly, the macrophage infiltration in the cortical interstitium increased after 3 days in UUO kidneys, but not untreated kidneys. After UUO developed, DBA/2j mice were injected i.v. with either IL-1ra(+) vehicle cells (IL-1ra-treated mice) or GC(+) vehicle cells (GC-treated mice) at 24 h after UUO. Six days after the injection of these vehicle cells, marked increase of CD11b(+) IL-1ra(+) vehicle cells was observed in the ICAM-1-positive interstitium of UUO kidneys from IL-1ra-treated mice. In contrast, no CD11b(+) IL-1ra(+) cells appeared in ICAM-1-negative contralateral kidneys from these mice. Furthermore, the infiltration of macrophages (p < 0.001), expression of ICAM-1 (p < 0.005), and presence of alpha-smooth muscle actin (p = 0.005) in the interstitium of UUO kidneys were significantly decreased in IL-1ra-treated mice compared with GC-treated mice. These findings suggest that IL-1 may contribute to the development of renal interstitial injury and that our method can deliver a functioning gene encoding an antiinflammatory cytokine gene specifically at that site by interacting with local adhesion molecules.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
166
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
609-16
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11123344-Animals, pubmed-meshheading:11123344-Antirheumatic Agents, pubmed-meshheading:11123344-Bone Marrow Cells, pubmed-meshheading:11123344-Bone Marrow Transplantation, pubmed-meshheading:11123344-Cell Movement, pubmed-meshheading:11123344-Disease Models, Animal, pubmed-meshheading:11123344-Female, pubmed-meshheading:11123344-Fibrosis, pubmed-meshheading:11123344-Gene Transfer Techniques, pubmed-meshheading:11123344-Intercellular Adhesion Molecule-1, pubmed-meshheading:11123344-Interleukin 1 Receptor Antagonist Protein, pubmed-meshheading:11123344-Interleukin-1, pubmed-meshheading:11123344-Kidney Cortex, pubmed-meshheading:11123344-Macrophage-1 Antigen, pubmed-meshheading:11123344-Macrophages, pubmed-meshheading:11123344-Mice, pubmed-meshheading:11123344-Mice, Inbred DBA, pubmed-meshheading:11123344-Nephritis, Interstitial, pubmed-meshheading:11123344-RNA, Messenger, pubmed-meshheading:11123344-Receptors, Interleukin-1, pubmed-meshheading:11123344-Sialoglycoproteins, pubmed-meshheading:11123344-Up-Regulation, pubmed-meshheading:11123344-Ureteral Obstruction
pubmed:year
2001
pubmed:articleTitle
Genetically modified bone marrow-derived vehicle cells site specifically deliver an anti-inflammatory cytokine to inflamed interstitium of obstructive nephropathy.
pubmed:affiliation
Department of Internal Medicine, Division of Nephrology, Jikei University School of Medicine, Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't