RGD Reference Report - Genetically modified bone marrow-derived vehicle cells site specifically deliver an anti-inflammatory cytokine to inflamed interstitium of obstructive nephropathy.

General

Genetically modified bone marrow-derived vehicle cells site specifically deliver an anti-inflammatory cytokine to inflamed interstitium of obstructive nephropathy.
Authors:	Yamagishi, H Yokoo, T Imasawa, T Mitarai, T Kawamura, T Utsunomiya, Y
Citation:	Yamagishi H, etal., J Immunol. 2001 Jan 1;166(1):609-16.
RGD ID:	6909121
Pubmed:	PMID:11123344 (View Abstract at PubMed)
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.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
ureteral obstruction		ISO	Il1rn (Mus musculus)	6909121; 6909121		RGD
ureteral obstruction		IMP		6909121		RGD

Objects Annotated

Genes (Rattus norvegicus)

Il1rn (interleukin 1 receptor antagonist)

Genes (Mus musculus)

Il1rn (interleukin 1 receptor antagonist)

Genes (Homo sapiens)

IL1RN (interleukin 1 receptor antagonist)

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Genetically modified bone marrow-derived vehicle cells site specifically deliver an anti-inflammatory cytokine to inflamed interstitium of obstructive nephropathy.